Oxime derivative and bactericide containing the same as active ingredient

ABSTRACT

A compound represented by general formula (I) or a salt thereof, a process for producing the same, an intermediate for the production thereof, and a bactericide (fungicide) containing the same as the active ingredient wherein R 1  represent optionally substituted aryl, optionally substituted heterocycle, mono- or di-substituted methyleneamino, optionally substituted (substituted imino)methyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, substituted carbonyl or substituted sulfonyl; R 2  represents alkyl, alkenyl, alkynyl or cycloalkyl; R 3  represents optionally substituted heterocycle; R 4  represents hydrogen, alkyl, alkoxy, halogen, nitro, cyano or haloalkyl; M represents oxygen, S(O)i (i being 0, 1 or 2), NR 16  (R 16  being hydrogen, alkyl or acyl) or a single bond; n represents 0 or 1, provided n represent 1 when R 3  represents imidazol-1-yl or 1H-1,2,4-triazol-1-yl; and the symbol˜represents the E form, Z form or a mixture thereof.

TECHNICAL FIELD

[0001] The present invention relates to an oxime derivative, particularly a heterocyclic compound substituted with α-(O-substituted oxyimino)-2-substituted benzyl, a process for producing it, intermediates therefor, and a bactericide (fungicide) containing it as an active ingredient.

BACKGROUND ART

[0002] Compounds containing α-(O-substituted oxyimino)-benzyl known so far include benzohydroxymoylazole derivatives having insecticidal activity (JP-A 1-308260, JP-A 5-1046, WO92/09581, JP-A 5-331011, JP-A 5-331012, JP-A 6-41086), oxime derivatives having insecticidal activity (JP-A 3-68559), 1-azolyl-substituted oxime ethers having fungicidal activity (JP-A 60-87269), etc.

[0003] The present invention is to provide a compound having more potent fungicidal activity, higher utility, etc., than the known compounds as well as low toxicity.

DISCLOSURE OF INVENTION

[0004] The present inventors have intensively studied to achieve the above object. As a result, it has been found that a heterocyclic compound substituted with α-(O-substituted oxyimino)-2-substituted benzyl has potent fungicidal activity. After further studies, the present invention has been completed.

[0005] The present invention provides:

[0006] 1. A compound of the formula (I):

[0007] wherein R¹ is optionally substituted aryl, an optionally substituted heterocyclic group, mono or disubstituted methyleneamino, optionally substituted (substituted imino)methyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, substituted carbonyl or substituted sulfonyl; R² is alkyl, alkenyl, alkynyl or cycloalkyl; R³ is an optionally substituted heterocyclic group; R⁴ is hydrogen, alkyl, alkoxy, halogen, nitro, cyano or halogenated alkyl; M is an oxygen atom, S(O)_(i) (in which i is 0, 1 or 2), NR¹⁶ (in which R¹⁶ is hydrogen, alkyl or acyl) or a single bond; n is 0 or 1, provided that, when R³ is imidazol-1-yl or 1H-1,2,4-triazol-1-yl, n is 1; and˜indicates an E- or Z-isomer or a mixture thereof; or a salt thereof;

[0008] 2. A compound according to the above item 1, wherein the optionally substituted heterocyclic group represented by R¹ is pyridyl, pyrimidinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, pyridazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, triazolyl, quinolyl, indolyl, benzisothiazolyl, benzisoxazolyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof;

[0009] 3. A compound according to the above item 1, wherein R¹ is phenyl or a heterocyclic group, each of which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro, or a salt thereof;

[0010] 4. A compound according to the above item 1, wherein R¹ is phenyl; phenyl substituted with halogen and/or lower alkyl; or pyridyl substituted with halogen and/or halogenated lower alkyl; or a salt thereof:

[0011] 5. A compound according to the above item 1, wherein R¹ is phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 4-chloro-2-methylphenyl, 2-chloropyridin-3-yl, 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl or 3-trifluoromethyl-5-chloropyridin-2-yl, or a salt thereof;

[0012] 6. A compound according to the above item 1, wherein R¹ is a group of the formula (a):

[0013] wherein R⁹ and R¹⁰ are the same or different and are hydrogen, optionally substituted alkyl, acyl, alkylthio, alkylsulfinyl alkylsulfonyl, optionally substituted amino, cycloalkyl, optionally substituted aryl or an optionally substituted heterocyclic group, or R⁹ and R¹⁰ are linked together to form a monocyclic or polycyclic ring which may contain a heteroatom, or a salt thereof;

[0014] 7. A compound according to the above item 1, wherein R⁹ and R¹⁰ are the same or different and are hydrogen, alkyl, haloalkyl, alkoxyalkyl, alkylcarbonyl, optionally substituted phenyl, optionally substituted naphthyl or an optionally substituted heterocyclic group, or R⁹ and R¹⁰ are linked together to form a cyclopentane or cyclohexane ring which may form a condensed ring with another ring, or a salt thereof;

[0015] 8. A compound according to the above item 1, wherein R⁹ is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl and cyano, or a salt thereof;

[0016] 9. A compound according to the above item 1, wherein R⁹ is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of chlorine, methyl, trifluoromethyl and methoxy, or a salt thereof;

[0017] 10. A compound according to the above item 1, wherein R⁹ is morpholino, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof;

[0018] 11. A compound according to the above item 1, wherein R¹⁰ is hydrogen or alkyl, or a salt thereof;

[0019] 12. A compound according to the above item 1, wherein R¹⁰ is hydrogen, methyl or ethyl, or a salt thereof;

[0020] 13. A compound according to the above item 1, wherein R² is alkyl or alkenyl, or a salt thereof;

[0021] 14. A compound according to the above item 1, wherein R² is methyl, ethyl or allyl, or a salt thereof;

[0022] 15. A compound according to the above item 1, wherein R³ is isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiazolinyl, isoxazolinyl, imidazolinyl, oxazolinyl or thiazolidinyl, each of which is unsubstituted or substituted, or a salt thereof;

[0023] 16. A compound according to the above item 1, wherein R³ is imidazolyl; imidazolyl substituted with lower alkyl; imidazolinyl; triazolyl; imidazolinyl substituted with lower alkyl; isoxazolyl; isoxazolyl substituted with lower alkyl; oxadiazolyl; oxadiazolyl substituted with lower alkyl; isoxazolinyl; isoxazolinyl substituted with lower alkyl; oxazolinyl; pyrazolyl; pyrazolyl substituted with lower alkyl; thiazolinyl; furyl; tetrazolyl substituted with lower alkyl; oxazolyl; isothiazolyl substituted with lower alkyl; thiazolidinyl; or thiazolidinyl substituted with lower alkyl; or a salt thereof;

[0024] 17. A compound according to the above item 1, wherein R³ is imidazol-1-yl, imidazol-2-yl, 1-methylimidazol-2-yl, 2-methylimidazol-1-yl, 4-methylimidazol-1-yl, 5-methylimidazol-1-yl, 2-imidazolin-2-yl, 1H-1,2,4-triazol-1-yl, 1-methyl-2-imidazolin-2-yl, isoxazol-3-yl, 3-methylisoxazol-5-yl, 5-methylisoxazol-3-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 2-isoxazolin-3-yl, 2-oxazolin-2-yl, 3-methyl-2-isoxazolin-5-yl, pyrazol-1-yl, 1-methylpyrazol-5-yl, 2-thiazolin-2-yl, 2-furyl, 3-methylisothiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 2-methyltetrazol-5-yl, oxazol-5-yl, isoxazol-5-yl, thiazolidin-2-yl or 3-methylthiazolidin-2-yl, or a salt thereof;

[0025] 18. A compound according to the above item 1, wherein R⁴ is hydrogen, or a salt thereof;

[0026] 19. A compound according to the above item 1, wherein M is an oxygen atom, or a salt thereof;

[0027] 20. A fungicidal composition comprising a compound according to any one of the above items 1 to 19 or a salt thereof as an active ingredient;

[0028] 21. A process for producing a compound of the formula (I):

[0029] wherein each symbol is as defined in the above item 1, which comprises reacting the compound of the formula (V):

[0030] wherein A is halogen and the other symbols are as defined in the above item 1, with a compound of the formula (X):

R³—H   (X)

[0031] wherein R³ is an optionally substituted heterocyclic group;

[0032] 22. A process according to the above item 21, wherein R³ is pyrrolyl, imidazolyl, pyrazolyl or triazolyl, each of which is unsubstituted or substituted;

[0033] 23. A compound of the formula (V):

[0034] wherein A is halogen and the other symbols are as defined in the above item 1, or a salt thereof;

[0035] 24. A compound according to the above item 23, wherein M is an oxygen atom, or a salt thereof;

[0036] 25. A compound of the formula (XIV):

[0037] wherein each symbol is as defined in the above item 1, provided that, when M is an oxygen atom and R³ is isoxazol-4-yl, n is 1, or a salt thereof;

[0038] 26. A compound according to the above item 25, wherein M is an oxygen atom, or a salt thereof; and,

[0039] 27. A compound of the formula (XLVIII):

[0040] wherein P is a protective group of a hydroxyl group, and the other symbols are as defined in the above item 1, or a salt thereof.

[0041] The term “lower” used herein means having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, unless otherwise indicated.

[0042] The aryl of the optionally substituted aryl represented by R¹ includes aryl having 6 to 14 carbon atoms such as phenyl, naphthyl, etc.

[0043] The optionally substituted heterocyclic group represented by R¹ includes unsubstituted or substituted heterocyclic groups. Examples of the heterocyclic group include 5- to 7-membered heterocyclic groups containing 1 to 4 heteroatoms selected from nitrogen, sulfur and oxygen in the ring, such as pyridyl (e.g., pyridin-2-yl, pyridin-3-yl), pyrimidinyl (e.g., pyrimidin-2-yl, pyrimidin-4-yl), benzoxazolyl (e.g., benzoxazol-2-yl), benzothiazolyl (e.g., benzothiazol-2-yl), benzimidazolyl, isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl), isothiazolyl, thiadiazolyl [e.g., 1,3,4-thiadiazolyl (e.g., 1,3,4-thiadiazol-2-yl), 1,2,4-thiadiazolyl, etc.], pyridazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl (e.g., 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, etc.), triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl, etc.), quinolyl (e.g., quinolin-2-yl), indolyl, benzisothiazolyl, benzisoxazolyl, pyrazinyl (e.g., pyrazin-2-yl), etc. The heterocyclic group may form a condensed cyclic group with a carbocycle or another heterocycle. The heterocycle has a bond to M at any possible position in the ring.

[0044] The substituent of the substituted aryl and substituted heterocyclic group represented by R¹ includes, for example, lower alkyl (e.g., methyl, ethyl, propyl, butyl, etc.), lower alkenyl (e.g., vinyl, allyl, crotyl, etc.), lower alkynyl (e.g., ethynyl, propargyl, butynyl, etc.), cycloalkyl (e.g., cyclopropyl, cyclopentyl, cyclohexyl, etc.), cycloalkenyl (e.g., cyclopentenyl, cyclohexenyl, etc.), lower alkanoyl (e.g., acetyl, propionyl, isobutyryl, etc.), lower alkylsilyl (e.g., methylsilyl, ethylsilyl, propylsilyl, butylsilyl, etc.), halogenated lower alkyl (e.g., trifluoromethyl, trichloromethyl, chloromethyl, 2-bromoethyl, 1,2-dichloropropyl, etc.), di(lower)alkylamino (e.g., dimethylamino, diethylamino, etc.), phenyl, phenyl(lower)alkyl (e.g., benzyl, phenethyl, etc.), phenyl(lower)alkenyl (e.g., styryl, cinnamyl, etc.), furyl(lower)alkyl (e.g., 3-furylmethyl, 2-furylethyl, etc.), furyl(lower)alkenyl (e.g., 3-furylvinyl, 2-furylallyl, etc.), halogen (e.g., fluorine, chlorine, bromine, iodine), nitro, cyano, lower alkylthio (e.g., methylthio, ethylthio, propylthio, etc.), —OR¹¹ [wherein R¹¹ is hydrogen, lower alkyl group (e.g., methyl, ethyl, propyl, etc.), lower alkenyl (e.g., vinyl, allyl, crotyl, etc.), lower alkynyl (e.g., ethynyl, 2-propynyl, 3-butynyl, etc.), lower alkanoyl (e.g., acetyl, propionyl, butyryl, etc.), phenyl, lower alkoxyphenyl (e.g., 3-methoxyphenyl, 4-ethoxyphenyl, etc.), nitrophenyl (e.g., 3-nitrophenyl, 4-nitrophenyl, etc.), phenyl(lower)alkyl (e.g., benzyl, phenethyl, phenylpropyl, etc.), cyanophenyl(lower)alkyl (e.g., 3-cyanophenylmethyl, 4-cyanophenylethyl, etc.), benzoyl, tetrahydropyranyl, pyridyl, trifluoromethylpyridyl, pyrimidinyl, benzothiazolyl, quinolyl, benzoyl(lower)alkyl (e.g., benzoylmethyl, benzoylethyl, etc.), benzensulfonyl, or lower alkylbenzenesulfonyl (e.g., toluenesulfonyl, etc.)], —CH₂—Z—R¹² [wherein Z is —O—, —S— or —NR¹³— (in which R¹³ is hydrogen or lower alkyl), R¹² is phenyl, halophenyl (e.g., 2-chlorophenyl, 4-fluorophenyl, etc.), lower alkoxyphenyl (e.g., 2-methoxyphenyl, 4-ethoxyphenyl, etc.), pyridyl, or pyrimidinyl], etc. In particular, halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro are preferred. More preferred are halogen and lower alkyl. The substituent may be at any possible position in the ring. The number of the substituent(s) is 1 to 5, preferably 1 to 4, more preferably 1 to 3. The substituents may be the same or different.

[0045] R¹ is preferably phenyl or a heterocyclic group each of which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro. Preferred examples of R¹ include phenyl, phenyl substituted with halogen (preferably chlorine) and/or lower alkyl (preferably methyl) (e.g., 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 4-chloro-2-methylphenyl, etc.), pyridyl substituted with halogen (preferably chlorine) and/or halogenated lower alkyl (preferably trifluoromethyl) (e.g., 2-chloropyridin-3-yl, 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl, 3-trifluoromethyl-5-chloropyridin-2-yl, etc.), etc.

[0046] Mono or disubstituted methyleneamino is also preferred for R¹. The mono or disubstituted methyleneamino is represented, for example, by the above formula (a). The alkyl of the optionally substituted alkyl represented by R⁹ or R¹⁰ in the formula (a) includes, for example, alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc. In particular, methyl or ethyl is preferred. Examples of the substituted alkyl include haloalkyl containing as the substituent at least one halogen (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine) (e.g., difluoromethyl, trifluoromethyl, chloromethyl, 2-bromoethyl, 2,3-dichloropropyl, etc.); alkoxyalkyl containing as the substituent alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.) (e.g., methoxymethyl, ethoxymethyl, methoxyethyl, etc.); etc. In particular, trifluoromethyl is preferred for the haloalkyl, and methoxymethyl is preferred for the alkoxyalkyl.

[0047] The acyl represented by R⁹ or R¹⁰ includes, for example, alkylcarbonyl, arylcarbonyl, etc. Examples of the alkylcarbonyl includes C₁₋₆ alkylcarbonyl, preferably C₁₋₄ alkylcarbonyl, such as acetyl, trifluoroacetyl, propionyl, butyryl, etc. Examples of the arylcarbonyl include C₆₋₁₄ arylcarbonyl such as benzoyl, naphthoyl, etc.

[0048] The alkyl of the alkylthio, alkylsulfinyl and alkylsulfonyl represented by R⁹ or R¹⁰ includes the above alkyl of the optionally substituted alkyl represented by R⁹ or R¹⁰.

[0049] The optionally substituted amino represented by R⁹ R¹⁰ includes, for example, amino, amino mono or disubstituted with alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., monomethylamino, dimethylamino, monoethylamino, etc.), amino monosubstituted with formyl, amino monosubstituted with alkylcarbonyl having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms (e.g., methylcarbonylamino, etc.), etc.

[0050] The cylcloalkyl represented by R⁹ or R¹⁰ includes cycloaklyl having 3 to 7 carbon atoms, preferably 5 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.

[0051] The optionally substituted aryl represented by R⁹ or R¹⁰ includes, for example, C₆₋₁₄ aryl such as phenyl, naphthyl (e.g., 1-naphthyl, etc.), fluorenyl, etc. In particular, phenyl is preferred. The aryl may be substituted at any possible position in the group. The number of the substituent(s) is 1 to 3. Examples the substituent include halogen, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl, cyano, etc.

[0052] Examples of the halogen as the substituent of the optionally substituted aryl represented by R⁹ or R¹⁰ include fluorine, chlorine, bromine, and iodine.

[0053] Examples of the optionally substituted alkyl as the substituent of the optionally substituted aryl represented by R⁹ or R¹⁰ include the optionally substituted alkyl represented by R¹ described hereinafter. Of them, alkyl or haloalkyl, in particular methyl or trifluoromethyl, is preferred.

[0054] Examples of the optionally substituted hydroxyl as the substituent of the optionally substituted aryl represented by R⁹ or R¹⁰ include hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, aryloxy, etc. The alkoxy includes, for example, alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, butoxy, etc. In particular, methoxy is preferred. The alkenyloxy includes, for example, alkenyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyloxy, allyloxy, crotyloxy, etc. In particular, allyloxy is preferred. The alkynyloxy includes, for example, alkynyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as ethynyloxy, propargyloxy, butynyloxy, etc. In particular, propargyloxy is preferred. The haloalkoxy includes alkoxy described above which is substituted with at least one halogen (e.g., fluorine, chlorine, bromine iodine) such as difluoromethoxy, trifluoromethoxy, chloromethoxy, etc. In particular, difluoromethoxy is preferred. The aryloxy includes, aryloxy having 6 to 12 carbon atoms, preferably 6 to 8 carbon atoms, such as phenoxy, naphthoxy, etc.

[0055] Examples of the alkylthio as the substituent of the optionally substituted aryl represented by R⁹ or R¹⁰ include alkylthio having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, more preferably 1 to 2 carbon atoms, such as methylthio, ethylthio, propylthio, butylthio, etc. In particular, methylthio is preferred.

[0056] Examples of the optionally substituted amino as the substituent of the optionally substituted aryl represented by R⁹ or R¹⁰ include amino, amino mono or disubstituted with alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., monomethylamino, dimethylamino, monoethylamino, etc.), etc.

[0057] The optionally substituted heterocyclic group represented by R⁹ or R¹⁰ includes, for example, heterocyclic groups containing 1 to 4, preferably 1 to 2 heteroatoms (e.g., oxygen, nitrogen, sulfur, etc.) in the ring. At any possible position in the ring, the heterocyclic group contains the bond to the methylene carbon atom in the formula (a). Examples of the heterocyclic group include morpholinyl, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl, pyrazinyl, etc. In particular, morpholinyl (e.g., morpholino, etc.), furyl (e.g., 2-furyl, etc.), thienyl (e.g., 2-thienyl, etc.), pyridyl (e.g., 2-pyridyl, etc.), pyrazinyl (e.g., 2-pyrazinyl, etc.), or pyrimidinyl (e.g., 2-pyrimidinyl, etc.) is preferred. The heterocyclic group is unsubstituted or substituted. Examples of the substituent include the above substituents of the optionally substituted aryl represented by R⁹ or R¹⁰.

[0058] The monocyclic or polycyclic ring which may contain a heteroatom and is formed by R⁹ and R¹⁰ is a 4 to 8 membered ring which is formed by R⁹ and R¹⁰ together with the carbon atom to which R⁹ and R¹⁰ are attached and which may contain at least one heteroatom (e.g., oxygen, nitrogen, sulfur, etc.). The ring may form a condensed ring with another ring. Examples of the monocyclic or polycyclic ring include cyclopentane, cyclohexane, indan, 1,2,3,4-tetrahydronaphthalene, 5,6,7,8-tetrahydroquinoline, 4,5,6,7-tetrahydrobenzo[b]furan, etc. At any possible position in the ring, the monocyclic or polycyclic ring contains the bivalent bond to the methyleneamino nitrogen atom.

[0059] R⁹ is preferably phenyl unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen (preferably chlorine), optionally substituted alkyl [e.g., alkyl (preferably in particular methyl), haloalkyl (preferably trifluoromethyl), alkoxyalkyl, etc.], optionally substituted hydroxyl [e.g., hydroxyl, alkoxy (preferably methoxy), alkenyloxy, alkynyloxy, haloalkoxy, aryloxy, etc.], alkylthio, optionally substituted amino, nitro, phenyl and cyano; or morpholino, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl or pyrazinyl, each of which is unsubstituted or substituted.

[0060] R¹⁰ is preferably hydrogen or alkyl (preferably methyl or ethyl).

[0061] The optionally substituted (substituted imino)methyl represented by R¹ is represented, for example, by the formula (b):

[0062] wherein R¹⁴ and R¹⁵ have the same meanings as the above R¹⁰ and R⁹, respectively.

[0063] The optionally substituted alkyl represented by R¹ includes, for example, alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc. In particular, methyl and ethyl are preferred. The substituted alkyl includes, for example, haloalkyl containing as the substituent at least one halogen atom (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine) (e.g., difluoromethyl, trifluoromethyl, chloromethyl, 2-bromoethyl, 2,3-dichloropropyl, etc.); alkoxyalkyl groups containing as the substituent alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.) (e.g., methoxymethyl ethoxymethyl, methoxyethyl, etc.), etc. In particular, trifluoromethyl is preferred for the haloalkyl, and methoxymethyl is preferred for the alkoxyalkyl.

[0064] The optionally substituted alkenyl represented by R¹ includes, for example, alkenyl having 2 to 8 carbon atoms, preferably 3 to 6 carbon atoms, such as allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, hexadienyl, etc. In particular, allyl is preferred. When the alkenyl is substituted, the substituent is, for example, halogen (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine), alkoxy having 1 to 8, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.), etc.

[0065] The alkynyl represented by R¹ includes, for example, alkynyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as propargyl, ethynyl, butynyl, etc. When the alkynyl is substituted, the substituent is, for example, halogen (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine), alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.), etc.

[0066] The substituted carbonyl represented by R¹ includes, for example, (optionally substituted alkyl)carbonyl, (optionally substituted aryl)carbonyl, (optionally substituted heterocyclic group)carbonyl, etc.

[0067] The substituted sulfonyl represented by R¹ includes, for example, (optionally substituted alkyl)sulfonyl, (optionally substituted aryl)sulfonyl, (optionally substituted heterocyclic group)sulfonyl, etc.

[0068] The optionally substituted alkyl, optionally substituted aryl and optionally substituted heterocyclic group in the substituted carbonyl or substituted sulfonyl include those represented by R¹ described above.

[0069] The alkyl represented by R² includes, for example, alkyl having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl propyl, isopropyl, butyl, isobutyl, t-butyl, etc. In particular, methyl or ethyl is preferred.

[0070] The alkenyl represented by R² includes, for example, alkenyl having 2 to 8 carbon atoms, preferably 3 to 6 carbon atoms, such as allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, hexadienyl, etc. In particular, allyl is preferred.

[0071] The alkynyl represented by R² includes, for example, alkynyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as propargyl, ethynyl, butynyl, etc.

[0072] The cycloalkyl represented by R² includes, for example, cycloalkyl having 3 to 8 carbon atoms, preferably 3 to 6 carbon atoms, such as cyclopropyl, cyclopentyl cyclohexyl, etc.

[0073] R² is preferably alkyl or alkenyl. In particular, methyl, ethyl and allyl are preferred.

[0074] The optionally substituted heterocyclic group represented by R³ includes unsubstituted or substituted heterocyclic groups. The heterocyclic group is a 5 to 7 membered heterocyclic group containing in the ring 1 to 4 heteroatoms selected from nitrogen, sulfur and oxygen. Examples of the heterocyclic group include isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl), oxazolyl (e.g., oxazol-2-yl, oxazol-5-yl), thiazolyl (e.g., thiazol-2-yl), isothiazolyl (e.g., isothiazol-5-yl), thiadiazolyl [e.g., 1,3,4-thiadiazolyl (e.g., 1,3,4-thiadiazol-2-yl), 1,2,4-thiadiazolyl, etc.], pyrrolyl, pyrazolyl (e.g., pyrazol-1-yl, pyrazol-5-yl), furyl (e.g., 2-furyl), thienyl (e.g., 2-thienyl), imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl), triazolyl [e.g., 1,2,4-triazolyl (e.g., 1H-1,2,4-triazol-1-yl, 4H-1,2,4-triazol-4-yl, 1,2,4-triazol-5-yl), etc.], tetrazolyl (e.g., 1H-tetrazol-5-yl, 2H-tetrazol-5-yl), oxadiazolyl [e.g., 1,3,4-oxadiazolyl (e.g., 1,3,4-oxadiazol-2-yl), 1,2,4-oxadiazolyl (e.g., 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl), etc.], thiazolinyl (e.g., 2-thiazolin-2-yl), isoxazolinyl (e.g., 2-isoxazolin-3-yl), imidazolinyl (e.g., 2-imidazolin-2-yl), oxazolinyl (e.g., 2-oxazolin-2-yl), thiazolidinyl, etc. The heterocyclic group may form a condensed ring with a carbocycle or another heterocycle. At any possible position, the heterocyclic group contains a bond to the oxime carbon atom in the formula (I).

[0075] Examples of the substituent of the substituted heterocyclic group represented by R³ include the above substituents of the substituted heterocyclic group represented by R¹. In particular, halogenated lower alkyl or lower alkyl is preferred.

[0076] R³ is preferably imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl, etc.), imidazolinyl (e.g., 2-imidazolin-2-yl, etc.), triazolyl (e.g., 1H-1,2,4-triazol-1-yl, etc.), isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl, etc.), oxazolyl (e.g., oxazol-2-yl, etc.), tetrazolyl (e.g., 1H-tetrazol-5-yl, etc.), oxadiazolyl (e.g., 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, etc.), isoxazolinyl (e.g., 2-isoxazolin-3-yl, 2-isoxazolin-5-yl, etc.), oxazolinyl (e.g., 2-oxazolin-2-yl, etc.), pyrazolyl (e.g., pyrazol-1-yl, pyrazol-5-yl, etc.), thiazolinyl (e.g., 2-thiazolin-2-yl, etc.), furyl (2-furyl, etc.), isothiazolyl (e.g., isothiazol-5-yl, etc.), thiazolidinyl (e.g., thiazolidin-2-yl, etc.), etc., each of which is unsubstituted or substituted.

[0077] R³ is more preferably imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl, etc.); imidazolyl substituted with lower alkyl (preferably methyl) (e.g., l-methylimidazol-2-yl, 2-methylimidazol-1-yl, 4-methylimidazol-1-yl, 5-methylimidazol-1-yl, etc.); imidazolinyl (e.g., 2-imidazolin-2-yl, etc.); triazolyl (e.g., 1H-1,2,4-triazol-1-yl, etc.); imidazolinyl substituted with lower alkyl (preferably methyl) (e.g., 1-methyl-2-imidazolin-2-yl, etc.); isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl, etc.); isoxazolyl substituted with lower alkyl (preferably methyl) (e.g., 3-methylisoxazol-5-yl, 5-methylisoxazol-3-yl, etc.); oxadiazolyl (e.g., 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, etc.); oxadiazolyl substituted with lower alkyl (preferably methyl or ethyl) (e.g., 5-methyl-1,2,4-oxadiazol-3-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, etc.); isoxazolinyl (e.g., 2-isoxazolin-3-yl, etc.); isoxazolinyl substituted with lower alkyl (preferably methyl) (e.g., 3-methyl-2-isoxazolin-5-yl, etc.); oxazolinyl (e.g., 2-oxazolin-2-yl, etc.); pyrazolyl (e.g., pyrazol-1-yl, etc.); pyrazolyl substituted with lower alkyl (preferably methyl) (e.g., 1-methylpyrazol-5-yl, etc.); thiazolinyl (e.g., 2-thiazolin-2-yl, etc.); furyl (e.g., 2-furyl, etc.); tetrazolyl substituted with lower alkyl (preferably methyl) (e.g., 2-methyltetrazol-5-yl, etc.); isothiazolyl substituted with lower alkyl (preferably methyl) (e.g., 3-methylisothiazol-5-yl, etc.); thiazolidinyl (e.g., thiazolidin-2-yl, etc.); thiazolidinyl substituted with lower alkyl (e.g., 3-methylthizolidin-2-yl, etc.), etc.

[0078] The alkyl represented by R⁴ includes the above alkyl represented by R².

[0079] The alkoxy represented by R⁴ includes, for example, alkoxy having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, etc.

[0080] The halogen represented by R⁴ includes, for example, fluorine, chlorine, bromine, and iodine.

[0081] The halogenated alkyl represented by R⁴ includes the above alkyl represented by R² which is substituted with at least one halogen (e.g., fluorine, chlorine, bromine, iodine), such as trifluoromethyl, etc.

[0082] R⁴ is preferably hydrogen.

[0083] The alkyl and acyl represented by R¹⁶ include the above alkyl and acyl represented by R⁹ or R¹⁰, respectively.

[0084] M is preferably an oxygen atom, sulfur atom or NR¹⁶, more preferably an oxygen atom.

[0085] When R³ is imidazol-1-yl or 1,2,4-triazol-1-yl, n is 1.

[0086] The compound of the present invention has two kinds of isomers: E and Z isomers. The present invention includes these isomers and mixtures of the isomers in any mixing ratios. This is herein indicated by the wave line (˜) in the formulas.

[0087] In addition, the compound of the present invention includes its hydrochloric acid salt, sulfuric acid salt, nitric acid salt, oxalic acid salt and p-toluenesulfonic acid salt.

[0088] Specific examples of the compound of the formula (I) of the present invention include compounds described in Examples hereinafter. Particularly preferred are the compounds of the formula (I) wherein

[0089] R¹ is phenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 1: Compound Nos. correspond to those in Examples hereinafter);

[0090] R¹ is 4-chlorophenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 7);

[0091] R¹ is 2-methylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 13);

[0092] R¹ is 4-methylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 15);

[0093] R¹ is 2-ethylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 16);

[0094] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 39);

[0095] R¹ is phenyl, R² is ethyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 61);

[0096] R¹ is phenyl, R² is allyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 81);

[0097] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 1-methylimidazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 136);

[0098] R¹ is 4-chloro-2-methylphenyl, R² is methyl, R³ is 1-methylimidazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 141);

[0099] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 336);

[0100] R¹ is 5-trifluoromethylpyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 387);

[0101] R¹ is 5-trifluoromethyl-3-chloropyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 390);

[0102] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 5-methylisoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 436);

[0103] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 3-methylisoxazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 636);

[0104] R¹ is 5-trifluoromethyl-3-chloropyridin-2-yl, R² is methyl, R³ is 3-methylisoxazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 690);

[0105] R¹ is 2-methylphenyl, R² is methyl, R³ is 1,3,4-oxadiazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 712);

[0106] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 1,3,4-oxadiazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 736);

[0107] R¹ is 4-chloro-2-methylphenyl, R² is methyl, R³ is 1,3,4-oxadiazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 741);

[0108] R¹ is 4-chlorophenyl, R² is methyl, R³ is 1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 807);

[0109] R¹ is 2-methylphenyl, R² is methyl, R³ is 1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 812);

[0110] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 836);

[0111] R¹ is 2-methylphenyl, R² is methyl, R³ is 5-methyl-1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 912);

[0112] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 5-methyl-1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 936);

[0113] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 1-methyl-2-imidazolin-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 1136);

[0114] R¹ is 4-chlorophenyl, R² is methyl, R³ is 1,2,4-oxadiazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 1584);

[0115] R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 2-methyl-2H-tetrazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2036);

[0116] R¹ is 3,5-dichloropyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2276);

[0117] R¹ is 5-chloro-3-trifluoromethylpyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2306);

[0118] R¹ is a group represented by the formula (a), R⁹ is 4-chlorophenyl, R¹⁰ is methyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2387);

[0119] R¹ is a group of by the formula (a), R⁹ is 3-trifluoromethylphenyl, R¹⁰ is methyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2399);

[0120] R¹ is a group of the formula (a), R⁹ is 3,4-dichlorophenyl, R¹⁰ is methyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2408);

[0121] R¹ is a group represented by the formula (a), R⁹ is 4-chlorophenyl, R¹⁰ is methyl, R² is methyl, R³ is 3-methylisoxazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2507);

[0122] R¹ is a group of the formula (a), R⁹ is 3-trifluoromethylphenyl, R¹⁰ is methyl, R² is methyl, R³ is thiazolidin-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2799); or

[0123] R¹ is a group of the formula (a), R⁹ is 3-trifluoromethylphenyl, R¹⁰ is methyl, R² is methyl, R³ is 3-methylthiazolidin-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2839).

[0124] The compound (I) (i.e., the compound of the formula (I); hereinafter the compounds of other formulas are sometimes abbreviated likewise) can be prepared, for example, according to the following synthetic routes.

[0125] [Route 1]

[0126] wherein A is halogen (e.g., chlorine, bromine, iodine, etc.), and the other symbols are as defined above.

[0127] The compound of the formula (IV) can be prepared by reacting the compound (IIa) with the compound (III) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0128] In this reaction, the amount of the compound (III) to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (IIa).

[0129] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.

[0130] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran (THF), dioxane, etc.), water, mixtures thereof, etc.

[0131] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 48 hours.

[0132] The compound (IV) thus obtained can be used in the next step as the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0133] The acid halide (Iha) used as the starting material in this reaction can be prepared according to JP-A 5-331124, for example, by halogenating the corresponding carboxylic acid with a thionyl halide (e.g., thionyl chloride, etc.), phosphoryl halide (e.g., phosphoryl chloride, etc.), phosgene, etc.

[0134] [Route 1 (continued)]

[0135] wherein each symbol is as defined above.

[0136] The compound of the formula (V) can be prepared by reacting the above compound (IV) with a halogenating agent in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0137] Examples of the halogenating agent to be used include thionyl halides (e.g., thionyl chloride, thionyl bromide, etc.), phosphoryl halides (e.g., phosphoryl chloride, phosphoryl bromide, etc.), phosphorus halides (e.g., phosphorus pentachloride, phosphorus trichloride, phosphorus pentabromide, phosphorus tribromide, etc.), phosgene, oxalyl halides (e.g., oxalyl chloride, etc.), triphenylphosphine/carbon tetrachloride, triphenylphosphine/carbon tetrabromide, etc. The amount of the halogenating agent to be used is 1 equivalent or more, preferably 1 to 4 equivalents.

[0138] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), nitrites (e.g., acetonitrile, etc.), mixed solvents thereof, etc.

[0139] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 120° C. The reaction time varies with the kind of compound, and is 0.1 to 48 hours.

[0140] The compound (V) thus obtained can be used in the next step as the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0141] [Route 1 (continued)]

[0142] wherein each symbol is as defined above.

[0143] The compound of the formula (VII) can be prepared by reacting the compound (VI) with the compound (III) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0144] The amount of the compound (III) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (VI).

[0145] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.

[0146] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), water, mixed solvents thereof, etc.

[0147] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 48 hours.

[0148] The compound (VII) thus obtained can be used in the next step as the reaction mixture or the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0149] The compound (VI) used as the starting material in this reaction can be prepared according to Takahashi et al. Tetrahedron Letters 22 (28), 2651-2654 (1981), for example, by halogenating the corresponding phthalide with triphenylphosphine dichloride, etc.

[0150] [Route 1 (continued)]

[0151] wherein each symbol is as defined above.

[0152] The compound of the formula (VIII) can be prepared by reacting the compound (VII) with a halogenating agent in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0153] Examples of the halogenating agent to be used include thionyl halides (e.g., thionyl chloride, thionyl bromide, etc.), phosphoryl halides (e.g., phosphoryl chloride, phosphoryl bromide, etc.), phosphorus halides (e.g., phosphorus pentachloride, phosphorus trichloride, etc.), phosgene, and oxalyl halides (e.g., oxalyl chloride, etc.). The amount of the halogenating agent to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0154] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), mixed solvents thereof, etc.

[0155] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 120° C. The reaction time varies with the kind of compound, and is 0.1 to 48 hours.

[0156] The compound (VIII) thus obtained can be used in the next step as the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0157] [Route 1 (continued)]

[0158] wherein each symbol is as defined above.

[0159] The compound of the formula (Va) can be prepared by reacting the compound (VIII) with the compound (IX) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0160] The amount of the compound (IX) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (VIII).

[0161] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.

[0162] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0163] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0164] The compound (Va) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0165] [Route 1 (continued)]

[0166] wherein each symbol is as defined above, and, in this reaction, R³ is preferably pyrrolyl (e.g., pyrrol-1-yl, etc.), imidazolyl (e.g., imidazol-1-yl, etc.), pyrazolyl (e.g., pyrazol-1-yl, etc.) or triazolyl (e.g., 1H-1,2,4-triazol-1-yl, etc.).

[0167] The compound of the formula (I) of the present invention can be prepared by reacting the compound (V) with the compound (X) in the presence or absence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0168] The amount of the compound (X) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (V).

[0169] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal hydrides (e.g., sodium hydride, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 5 equivalents.

[0170] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethate, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0171] The reaction temperature is −30° C. to 170° C., preferably −10° C. to 140° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0172] If necessary, the desired compound (I) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0173] [Route 2]

[0174] wherein Z is lithium or magnesium halide (e.g., −MgBr, −MgI, etc.), L is halogen (e.g., chlorine, bromine, iodine, etc.), alkoxy (e.g., lower alkoxy such as methoxy, ethoxy, propoxy, etc.), imidazol-1-yl or N-methyl-N-methoxyamino, R³ is an optionally substituted heterocyclic group, and the other symbols are as defined above.

[0175] The compound of the formula (XIV) can be prepared by reacting the compound (XI) with the compound (XII) or (XIII) in an appropriate solvent (alone or as a mixture).

[0176] The amount of the compound (XII) or (XIII) to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XI).

[0177] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), triethylamine, mixed solvents thereof, etc.

[0178] The reaction temperature is −100° C. to 100° C., preferably −80° C. to 40° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0179] The compound (XIV) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0180] The compound (XI) used as the starting material in this reaction can be prepared according to JP-A 3-246268 or JP-A 5-97768, for example, by reacting a compound corresponding to the compound (XI) wherein the moiety Z is halogen with butyl lithium or magnesium.

[0181] [Route 2 (continued)]

[0182] wherein each symbol is as defined above.

[0183] The compound of the formula (XIV) can be prepared by reacting the compound (II) with the compound (XV) in an appropriate solvent (alone or as a mixture).

[0184] The amount of the compound (XV) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (II).

[0185] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), triethylamine, mixed solvents thereof, etc.

[0186] The reaction temperature is −100° C. to 100° C., preferably −80° C. to 40° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0187] The compound (XIV) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0188] The compound (XV) can be prepared by reference to A. R. Katritzky, Handbook of Heterocyclic Chemistry, 360-361 (1985), for example, by lithiating the corresponding heterocyclic compound with butyl lithium, etc., or by reacting the corresponding halogenated heterocyclic compound with magnesium.

[0189] [Route 2 (continued)]

[0190] wherein each symbol is as defined above.

[0191] The compound of the formula (I) of the present invention can be prepared by reacting the compound (XIV) with the compound (III) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in an appropriate solvent (alone or as a mixture).

[0192] The amount of the compound (III) to be used in this reaction is 1 equivalent or more, preferably 1 to 4 equivalents, based on the compound (XIV).

[0193] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.

[0194] The reaction temperature is 0° C. to 160° C., preferably 60° C. to 130° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0195] If necessary, the desired compound (I) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0196] [Route 2 (continued)]

[0197] wherein each symbol is as defined above.

[0198] The compound of the formula (XVI) can be prepared by reacting the compound (XIV) with hydroxylamine or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in an appropriate solvent (alone or as a mixture).

[0199] The amount of the hydroxylamine or a salt thereof to be used in this reaction is 1 equivalent or more, preferably 1 to 4 equivalents, based on the compound (XIV).

[0200] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.

[0201] The reaction temperature is 0° C. to 160° C., preferably 60° C. to 130° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0202] The compound (XVI) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0203] [Route 2 (continued)]

[0204] wherein Y is halogen (e.g., chlorine, bromine, iodine, etc.), alkylsulfonyloxy (e.g., lower alkylsulfonyloxy such as methylsulfonyloxy, ethylsulfonyloxy, etc.) or alkoxysulfonyloxy (e.g., lower alkoxysulfonyloxy such as methoxysulfonyloxy, ethoxysulfonyloxy, etc.), and the other symbols are as defined above.

[0205] The compound of the formula (I) of the present invention can be prepared by reacting the compound (XVI) with the compound (XVII) in the presence of a base in an appropriate solvent (alone or as a mixture).

[0206] The amount of the compound (XVII) to be used in this reaction is 1 equivalent, preferably 1 to 2 equivalents, based on the compound (XVI).

[0207] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0208] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0209] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0210] If necessary, the desired compound (I) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0211] [Route 3]

[0212] wherein R⁵ is hydrogen or alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.), and the other symbols are as defined above.

[0213] The compound of the formula (XX) can be prepared by reacting the compound (XVIII) with the compound (XIX) in the absence of a solvent or in an appropriate solvent (alone or as a mixture), for example, by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).

[0214] The amount of the compound (XIX) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XVIII).

[0215] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), mixed solvents thereof, etc.

[0216] The reaction temperature is 0° C. to 180° C., preferably 20° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0217] The compound (XX) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0218] The compound (XVIII) used as the starting material in this reaction can be prepared, for example, according to JP-A 3-246268 or JP-A 5-97768, for example, by reacting the corresponding carboxylic acid ester with ammonia or by subjecting the corresponding α-ketoamide to oximation.

[0219] [Route 3 (continued)]

[0220] wherein R⁶ is hydrogen or alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.), and the other symbols are as defined above.

[0221] The compound of the formula (Ia) of the present invention can be prepared by reacting the compound (XX) with the compound (XXI) in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).

[0222] The amount of the compound (XXI) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XX).

[0223] Examples of the acid to be used include aliphatic carboxylic acids (e.g., acetic acid, etc.). The amount of the acid to be used is 1 equivalent or more, preferably 5 to 50 equivalents, based on the compound (XX).

[0224] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.

[0225] The reaction temperature is 0° C. to 180° C., preferably 20° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0226] If necessary, the desired compound (Ia) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0227] [Route 4]

[0228] wherein each symbol is as defined above.

[0229] The compound of the formula (XXII) can be prepared by reacting the compound (XX) with hydroxylamine in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).

[0230] The amount of the hydroxylamine to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XX).

[0231] Examples of the acid to be used include aliphatic carboxylic acids (e.g., acetic acid, etc.). The amount of the acid to be used is 1 equivalent or more, preferably 5 to 50 equivalents, based on the compound (XX).

[0232] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), water, mixed solvents thereof, etc.

[0233] The reaction temperature is −10° C. to 120° C., preferably 0° C. to 80° C. The reaction time varies with the kind of compound, and is 0.1 to 40 hours.

[0234] The compound (XXII) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0235] [Route 4 (continued)]

[0236] wherein each symbol is as defined above.

[0237] The compound of the formula (Ib) of the present invention can be prepared by subjecting the compound (XXII) to ring closure reaction in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).

[0238] Examples of the acid to be used include aliphatic carboxylic acids (e.g., acetic acid, etc.). The amount of the acid to be used is 1 equivalent or more, preferably 5 to 50 equivalents, based on the compound (XXII).

[0239] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.

[0240] The reaction temperature is 20° C. to 180° C., preferably 50° C. to 140° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0241] If necessary, the desired compound (Ib) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0242] [Route 5]

[0243] wherein each symbol is as defined above.

[0244] The compound of the formula (Ib) of the present invention can be prepared by reacting the compound (XXIII) with the compound (XXIV) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to S. Chiou et al., J. Heterocyclic Chem., 26, 125 (1989).

[0245] The amount of the compound (XXIV) to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XXIII).

[0246] Examples of the base to be used include amines (e.g., pyridine, triethylamine, etc.). The amount of the base to be used is 1 equivalent or more, preferably 3 to 20 equivalents, based on the compound (XXIII).

[0247] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.

[0248] The reaction temperature is 20° C. to 180° C., preferably 50° C. to 140° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0249] If necessary, the desired compound (Ib) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0250] The compound (XXIII) used as the starting material in this reaction can be prepared, for example, according to Japanese Patent Application No. 5-56143, for example, by subjecting the corresponding α-methoxyimino(substituted)-benzyl cyanide to hydrolysis with a base (e.g., sodium hydroxide, potassium hydroxide, etc.) to give a carboxylic acid, and then halogenating the carboxylic acid with a thionyl halide (e.g., thionyl chloride, etc.), phosphoryl halide (e.g., phosphoryl chloride, etc.), etc.

[0251] [Route 6]

[0252] wherein R⁷ is alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.), and the other symbols are as defined above.

[0253] The compound of the formula (XXVI) can be prepared by reacting the compound (XXV) with a monohydrate of the compound (XXIa) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in an appropriate solvent (alone or as a mixture).

[0254] The amount of the compound (XXIa) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XXV).

[0255] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), ethers (e.g., THF, dioxane, etc.), water, mixed solvents thereof, etc.

[0256] The reaction temperature is 0° C. to 160° C., preferably 10° C. to 130° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0257] The compound (XXVI) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0258] The compound (XXV) used as the starting material in this reaction can be prepared, for example, according to JP-A 4-295454, for example, by subjecting the corresponding α-ketocarboxylic acid ester or a ketal at the α-position of the ester to oximation.

[0259] [Route 6 (continued)]

[0260] wherein each symbol is as defined above.

[0261] The compound of the formula (Ic) of the present invention can be prepared by reacting the compound (XXVI) with the compound (XXVII) in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to C. Ainaworth, J. Am. Chem. Soc., 77, 1148 (1955).

[0262] The amount of the compound (XXVII) to be used in this reaction is 1 equivalent or more, preferably 1 to 20 equivalents, based on the compound (XXVI).

[0263] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.

[0264] The reaction temperature is 20° C. to 200° C., preferably 50° C. to 170° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0265] If necessary, the desired compound (Ic) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0266] [Route 7]

[0267] wherein each symbol is as defined above.

[0268] The compound of the formula (XXIX) can be prepared by reacting the compound (XXVIII) with hydroxylamine or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in the presence or absence of a base in an appropriate solvent (alone or as a mixture).

[0269] The amount of the hydroxylamine or a salt thereof to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XXVIII).

[0270] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0271] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.

[0272] The reaction temperature is 0° C. to 160° C., preferably 20° C. to 110° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0273] The compound (XXIX) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0274] The compound (XXVIII) used as the starting material in this reaction can be prepared, for example, according to Route 13, 14 or 15, or Japanese Patent Application No. 4-324120, for example, by introducing the cyano moiety to the corresponding (substituted)benzyl halide using an alkaline metal cyanide (e.g., sodium cyanide, etc.), and then subjecting the resulting compound to oximation.

[0275] [Route 7 (continued)]

[0276] wherein each symbol is as defined above except that R⁵ of the compound (XXX) is other than hydrogen and preferably lower alkyl such as methyl, ethyl, propyl, etc.

[0277] The compound of the formula (Id) of the present invention can be prepared by reacting the compound (XXIX) with the compound (XXVII) or (XXX) in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to U.S. Pat. No. 3,910,942.

[0278] The amount of the compound (XXVII) or (XXX) to be used in this reaction is 1 equivalent or more, preferably 1 to 20 equivalents, based on the compound (XXIX).

[0279] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.

[0280] The reaction temperature is 40° C. to 200° C., preferably 60° C. to 180° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0281] If necessary, the desired compound (Id) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0282] The compounds of the formulas (Ie), (If) and (Ig) of the present invention can be prepared according to the following Route 8.

[0283] [Route 8]

[0284] wherein each symbol is as defined above.

[0285] The compound of the formula (Ie) of the present invention can be prepared by reacting the compound (XXVIII) with an azide compound in the presence of ammonium chloride in an appropriate solvent (alone or as a mixture) by reference to K. Kubo, J. Med. Chem., 36, 2182 (1993).

[0286] Examples of the azide compound to be used include alkaline metal azides (e.g., sodium azide, potassium azide, etc.), etc. The amount of the azide compound to be used is 1 equivalent or more, preferably 1 to 15 equivalents, based on the compound (XXVIII). The amount of the ammonium chloride to be used is 1 equivalent or more, preferably 1 to 15 equivalents, based on the compound (XXVIII).

[0287] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), ethers (e.g., dioxane, etc.), mixed solvents thereof, etc.

[0288] The reaction temperature is 40° C. to 200° C., preferably 60° C. to 180° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0289] The desired compound (le) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0290] [Route 8 (continued)]

[0291] wherein each symbol is as defined above.

[0292] The compound of the formula (If) or (Ig) of the present invention can be prepared by reacting the compound (Ie) with the compound (XXXI) in the presence of a base in an appropriate solvent (alone or as a mixture).

[0293] The amount of the compound (XXXI) be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (Ie).

[0294] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.

[0295] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0296] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with-the kind of compound, and is 0.5 to 90 hours.

[0297] If necessary, the desired compound (If) and (Ig) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0298] The compounds of the formulas (Ih) and (Ii) of the present invention can be prepared according to the following Route 9.

[0299] [Route 9]

[0300] wherein each symbol is as defined above.

[0301] The compound of the formula (XXXII) can be prepared by reacting the compound (XXVIII) with methanol in the presence of an acid by reference to, for example, JP-A 5-271223.

[0302] The amount of the methanol to be used in this reaction is 1 equivalent or more, preferably 1 to 1.2 equivalents, based on the compound (XXVIII).

[0303] Examples of the acid to be used include hydrochloric acid, hydrobromic acid, etc. The amount of the acid to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXVIII).

[0304] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, ethyl ether, etc.), mixed solvents thereof, etc.

[0305] The reaction temperature is −30° C. to 150° C., preferably 0° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0306] The compound (XXXII) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0307] [Route 9 (continued)]

[0308] wherein each symbol is as defined above.

[0309] The compound of the formula (XXXIV) can be prepared by reacting the compound (XXXII) or a salt thereof (e.g., hydrochloric acid, hydrobromic acid, etc.) with the compound (XXXIII) by reference to, for example, JP-A 5-271223.

[0310] The amount of the compound (XXXIII) to be used in this reaction is 1 equivalent or more, preferably 1 to 1.2 equivalents, based on the compound (XXXII).

[0311] Examples of the solvent to be used include alcohols (e.g., methanol, ethanol, propanol, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.

[0312] The reaction temperature is −30° C. to 150° C., preferably 0° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0313] The compound (XXXIV) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0314] [Route 9 (continued)]

[0315] wherein each symbol is as defined above.

[0316] The compound of the formula (Ih) of the present invention can be prepared by subjecting the compound (XXXIV) or a salt thereof (e.g., hydrochloric acid, hydrobromic acid, etc.) to ring closure reaction in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to, for example, JP-A 5-271223.

[0317] Examples of the acid to be used include hydrochloric acids, hydrobromic acid, etc. The amount of the acid to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXIV).

[0318] Examples of the solvent to be used include alcohols (e.g., methanol, ethanol, propanol, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.

[0319] The reaction temperature is 10° C. to 150° C., preferably 30° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0320] If necessary, the desired compound (Ih) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0321] [Route 9 (continued)]

[0322] wherein each symbol is as defined above.

[0323] The compound of the formula (Ii) of the present invention can be prepared by reacting the compound (Ih) with the compound (XXXI) in the presence of a base in an appropriate solvent (alone or as a mixture).

[0324] The amount of the compound (XXXI) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (Ih).

[0325] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0326] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0327] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0328] If necessary, the desired compound (Ii) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0329] The compound of the formula (Ij) of the present invention can be prepared according to the following Route 10.

[0330] [Route 10]

[0331] wherein W is oxygen, sulfur or N—R⁵, and R⁵ and the other symbols are as defined above.

[0332] The compound of the formula (Ij) of the present invention can be prepared by reacting the compound (XXVIII) with the compound (XXXV) or a salt thereof (e.g., hydrochloric acid salt, hydrobromic acid salt, etc.) in the presence or absence of a base in the presence or absence of a metal salt in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Doris P. Schumacher et al., J. Org. Chem., 55, 5291 (1990).

[0333] The amount of the compound (XXXV) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XXVIII).

[0334] Examples of the base to be used include amines (e.g., triethylamine, etc.). The amount of the base to be used is 1 equivalent or more, preferably 1 to 6 equivalents, based on the compound (XXVIII).

[0335] Examples of the metal salt to be used include potassium carbonate, zinc acetate, etc. The amount of the metal salt to be used is 0.01 to 0.5 equivalent, preferably 0.02 to 0.2 equivalent, based on the compound (XXVIII).

[0336] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), alcohols (e.g., butanol, 2-methoxyethanol, ethylene glycol, glycerol, etc.), mixed solvents thereof, etc.

[0337] The reaction temperature is 20° C. to 200° C., preferably 50° C. to 160° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0338] If necessary, the desired compound (Ij) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0339] The compound of the formula (Ik) of the present invention can be prepared according to the following Route 11.

[0340] [Route 11]

[0341] wherein each symbol is as defined above.

[0342] The compound of the formula (XXXVI) can be prepared by reacting the compound (XXVIII) or the compound (XXV) with a reducing agent in an appropriate solvent (alone or as a mixture) by reference to, for example, L.-F Tietze and Th. Eicher, “Reaktionen und Synthesen im organisch-chemischen Praktikum”, pp. 84-97 (1981).

[0343] Examples of the reducing agent to be used include alkylaluminum hydrides (e.g., diisobutylaluminum hydride, etc.). The amount of the reducing agent to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0344] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, ethyl ether, etc.), mixed solvents thereof, etc.

[0345] The reaction temperature is −100° C. to 80° C., preferably −70° C. to 30° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0346] The compound (XXXVI) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0347] [Route 11 (continued)]

[0348] wherein each symbol is as defined above.

[0349] The compound of the formula (Ik) of the present invention can be prepared by reacting the compound (XXXVI) with the compound (XXXVII) in the presence of a base in an appropriate solvent (alone or as a mixture) according to, for example, JP-A 58-131984.

[0350] The amount of the compound (XXXVII) to be used in this reaction is I equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXVI).

[0351] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0352] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), mixed solvents thereof, etc.

[0353] The reaction temperature is 30° C. to 150° C., preferably 50° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0354] If necessary, the desired compound (Ik) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0355] The compound of the formula (In) of the present invention can be prepared according to the following Route 12.

[0356] [Route 12]

[0357] wherein R⁸ is hydrogen, alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.) or halogen (e.g., fluorine, chlorine, bromine, iodine), and the other symbols are as defined above.

[0358] The compound of the formula (XXXIXa) can be prepared by reacting the compound (XXXVIII) with a Lewis acid in an appropriate solvent (alone or a mixture).

[0359] The compound (XXXVIII) is synthesized by a modified method of Routes 1 to 11.

[0360] Examples of the Lewis acid to be used include aluminium chloride, aluminium bromide, boron trifluoride, boron trichloride, ferric chloride, etc.

[0361] The amount of the Lewis acid to be used is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XXXVIII).

[0362] Examples of the solvent to be used include anisole, nitromethane, nitroethane, mixed solvents thereof, etc.

[0363] The reaction temperature is −30° C. to 120° C., preferably −10° C. to 80° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0364] Alternatively, the compound (XXXIXa) can be prepared by reacting the compound (XXXVIII) with hydrogen in the presence of a catalyst in an appropriate solvent (alone or as a mixture).

[0365] The amount of the hydrogen to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXVIII).

[0366] Examples of the catalyst to be used include palladium-carbon, etc. The amount of the catalyst to be used is 0.01 equivalent or more, preferably 0.01 to 0.2 equivalent, based on the compound (XXXVIII).

[0367] Examples of the solvent to be used include ethyl acetate, alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.

[0368] The reaction temperature is −30° C. to 120° C., preferably −10° C. to 80° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0369] The compound (XXXIXa) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0370] [Route 12 (continued)]

[0371] wherein each symbol is as defined above.

[0372] The compound of the formula (In) of the present invention can be prepared by reacting the compound (XXXIX) with the compound (XL) in the presence of a base in an appropriate solvent (alone or as a mixture).

[0373] The amount of the compound (XL) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXIX).

[0374] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0375] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.); halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0376] The reaction temperature is 0° C. to 190° C., preferably 10° C. to 160° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0377] If necessary, the desired compound (In) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0378] The compound (XXVIII) which can be used as the starting material in the above Schemes 19, 21, 23, 27 and 28 can be prepared according to the following Route 13, 14 or 15.

[0379] [Route 13]

[0380] wherein each symbol is as defined above.

[0381] The compound of the formula (XXVIII) can be prepared by reacting the compound (V) with an alkaline metal cyanide (e.g., sodium cyanide, potassium cyanide, etc.) in an appropriate solvent (alone or as a mixture).

[0382] The amount of the alkaline metal cyanide to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (V).

[0383] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0384] The reaction temperature is 0° C. to 190° C., preferably 20° C. to 160° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0385] The compound (XXVIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.

[0386] [Route 14]

[0387] wherein each symbol is as defined above.

[0388] The compound of the formula (XXVIII) can be prepared by reacting the compound (XVIII) with an acid anhydride in the presence or absence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to, for example, J. Goto et al., J. Antibiotics, 37, 557 (1984).

[0389] Examples of the acid anhydride to be used include acetic anhydride, trifluoroacetic anhydride, etc. The amount of the acid anhydride to be used is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XVIII).

[0390] Examples of the base to be used include amines (e.g., pyridine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 30 equivalents, based on the compound (XVIII). Examples of the solvent to be used is aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g. cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), mixed solvents thereof, etc.

[0391] The reaction temperature is −30° C. to 160° C., preferably −10° C. to 110° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0392] The compound (XXVIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0393] [Route 15]

[0394] wherein R⁴ is as defined above.

[0395] The compound of the formula (XLII) can be prepared by reacting the compound (XLI) with an alkyl nitrite in the presence of a base in an appropriate solvent (alone or as a mixture) in the presence or absence of a phase-transfer catalyst.

[0396] Examples of the alkyl nitrite to be used include methyl nitrite, ethyl nitrite, propyl nitrite, isopropyl nitrite, butyl nitrite, isoamyl nitrite, etc. The amount of the alkyl nitrite to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0397] Examples of the phase-transfer catalyst to be used include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium hydrogensulfate, tetramethylammonium bromide, benzyltriethylammonium chloride, tris(3,6-dioxaheptyl)amine, etc. The amount of the phase-transfer catalyst to be used is 0.005 to 0.5 equivalent, preferably 0.01 to 0.2 equivalent.

[0398] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0399] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), alcohols (e.g., methanol, butanol, etc.), water, mixed solvents thereof, etc.

[0400] The reaction temperature is −10° C. to 120° C., preferably 0° C. to 80° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0401] The compound (XLII) or a salt thereof (e.g., sodium salt, potassium salt, etc.) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0402] The compound (XLI) used as the starting material in this reaction is commercially available from Aldrich.

[0403] [Route 15 (continued)]

[0404] wherein each symbol is as defined above.

[0405] The compound of the formula (XLIII) can be prepared by reacting the compound (XLII) or a salt thereof (e.g., sodium salt, potassium salt, etc.) with the compound (XVII) in the presence or absence of a base in the presence or absence of a phase-transfer catalyst in an appropriate solvent (alone or as a mixture).

[0406] The amount of the compound (XVII) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XLII).

[0407] Examples of the phase-transfer catalyst to be used include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium hydrogensulfate, tetramethylammonium bromide, benzyltriethylammonium chloride, tris(3,6-dioxaheptyl)amine, etc. The amount of the phase-transfer catalyst to be used is 0.005 to 0.5 equivalent, preferably 0.01 to 0.2 equivalent.

[0408] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0409] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0410] The reaction temperature is −20° C. to 140° C., preferably 10° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0411] The compound (XLIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0412] [Route 15 (continued)]

[0413] wherein each symbol is as defined above.

[0414] The compound of the formula (XLIV) can be prepared by reacting the compound (XLIII) with a halogenating agent in the presence of a reaction initiator in an appropriate solvent (alone or as a mixture).

[0415] Examples of the halogenating agent to be used include halogenated succinimide (e.g., N-chlorosuccinimide, N-bromosuccinimide, etc.), chlorine, and bromine. The amount of the halogenating agent to be used is 1 equivalent or more, preferably 1 to 1.5 equivalent.

[0416] Examples of the reaction initiator to be used include peroxides (e.g., benzoyl peroxide, etc.), azobisisobutyronitrile, etc. The amount of the reaction initiator to be used is 0.01 equivalent or more, preferably 0.03 to 0.3 equivalent.

[0417] Examples of the solvent to be used include aromatic hydrocarbons (e.g., benzene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., carbon tetrachloride, 1,2-dichloroethane, etc.), mixed solvents thereof, etc.

[0418] The reaction temperature is 20° C. to 160° C., preferably 50° C. to 120° C. The reaction time varies with the kind of compound, and is 0.1 to 48 hours.

[0419] The compound (XLIV) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0420] [Route 15 (continued)]

[0421] wherein each symbol is as defined above.

[0422] The compound of the formula (XXVIIIa) can be prepared by reacting the compound (XLIV) with the compound (IX) in the presence of a base in the presence or absence of a phase-transfer catalyst in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0423] The amount of the compound (IX) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XLIV).

[0424] Examples of the phase-transfer catalyst to be used include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium hydrogensulfate, tetramethylammonium bromide, benzyltriethylammonium chloride, tris(3,6-dioxaheptyl)amine, etc. The amount of the phase-transfer catalyst to be used is 0.005 to 0.5 equivalent, preferably 0.01 to 0.2 equivalent.

[0425] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0426] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0427] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0428] The compound (XXVIIIa) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0429] The compound (XXXIX) which can be used as the starting material in Scheme 31 described above can also be prepared according to the following Route 16.

[0430] [Route 16]

[0431] wherein P is a protective group of a hydroxyl group, and the other symbols are as defined above.

[0432] The compound (XLVI) can be prepared by protecting the hydroxyl group of the commercially available compound (XLV) with an appropriate protective group.

[0433] The hydroxyl group can be protected with a group represented by P by a conventional method for protecting a hydroxyl group described in, for example, T. W. Green, “Protective Groups in Organic Synthesis”, p. 1-113, John Willy & Sons (1981); C. B. Reese, “Protective Groups in Organic Chemistry”, J. F. McOmie (ed.), p.95-143, Plenum Press (1973), etc.

[0434] For example, the compounds (XLVI) protected with tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydrothiofuranyl, 1-ethoxyethyl and 1-methyl-1-methoxyethyl can be prepared by reacting the compound (XLV) with the corresponding olefins in the presence of an acid catalyst in an appropriate solvent or in the absence of a solvent.

[0435] The corresponding olefins are 3,4-dihydro-2H-pyran, 2,3-dihydro-4H-thiin, dihydrofuran, dihydrothiofuran, ethyl vinyl ether, and 2-methoxypropene, respectively, and they are commercially available or can be prepared by known methods.

[0436] The amount of the olefin to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the compound (XLV).

[0437] Examples of the acid catalyst include hydrogen chloride, phosphorus oxychloride, p-toluenesulfonic acid, p-toluenesulfonic acid pyridine salt, montmorillonite, bistrimethyl sulfate, acetic acid, p-toluenesulfonic acid polyvinyl pyridinium, trifluoroacetic acid, boron trifluoride etherate (BF₃·OEt₂) and acidic ion-exchange resins, etc.

[0438] When a solvent is used, non-alcoholic solvents can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), ethers (e.g., diethyl ether, tetrahydrofuran, dioxane, etc.), esters (e.g., ethyl acetate, etc.), N,N-dimethylformamide, mixed solvents thereof, etc.

[0439] The reaction temperature is −30° C. to 100° C., preferably 0° C. to 60° C. The reaction time is normally 15 minutes to 24 hours.

[0440] The compound (XLVI) protected with a silyl enol type protective group can be obtained by reacting the compound (XLV) with an appropriate silylating agent. In general, it can be obtained by reacting the compound (XLV) with chlorosilane in the presence of a base in an appropriate solvent.

[0441] Chlorosilane is commercially available or can be prepared by a known method.

[0442] The amount of the chlorosilane to be used is 1 to 5 equivalents, preferably 1 to 2 equivalents, based on the compound (XLV).

[0443] Examples of the base to be used include organic bases (e.g., N,N-dimethylaniline, pyridine, triethylamine, imidazole, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal hydrides (e.g., sodium hydride, potassium hydride, etc.), metal bicarbonates (e.g., sodium bicarbonate, potassium bicarbonate, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0444] Examples of the solvent to be used include hydrocarbons (e.g., hexane, benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), ethers (e.g., diethyl ether, tetrahydrofuran, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g., acetonitrile, etc.), N,N-dimethylformamide, dimethyl sulfoxide, mixed solvents thereof, etc.

[0445] The reaction temperature is −20° C. to 100° C., preferably 0° C. to 60° C.

[0446] The reaction time is 5 minutes to 30 hours, preferably 30 minutes to 15 hours.

[0447] The compound (XLVI) protected with methoxymethyl or triphenylmethyl and the compound (XLVI) protected with tetrahydrofuranyl or 1-ethoxyethyl described above can be obtained by reacting the compound (XLV) with the corresponding halide in the presence of a base.

[0448] The corresponding halides are halomethyl methyl ether, triphenylmethyl halide, 2-halotetrahydrofuran and 1-haloethyl ether, respectively, and they are commercially available or can be prepared by a known method.

[0449] Examples of the halide to be used include chlorides, and bromides.

[0450] The amount of the halide to be used, the kind of base and solvent, and the reaction conditions, etc., are similar to those in the above reaction of the compound (XLV) with chlorosilane.

[0451] Alternatively, the compound (XLVI) protected with methoxymethyl described above can also be obtained by reacting the compound (XLV) with dimethoxymethane in the presence of an appropriate catalyst (e.g., phosphorus pentaoxide, etc.).

[0452] The solvent to be used and the reaction conditions are similar to those in the reaction of the compound (XLV) with olefin.

[0453] The compound (XLVI) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0454] [Route 16 (continued)]

[0455] wherein each symbol is as defined above.

[0456] The compound (XLVII) can be prepared by reacting the compound (XLVI) with lithium or magnesium in an appropriate solvent.

[0457] The amount of the lithium or magnesium to be used is 1 to 4 equivalents, preferably 1 to 2 equivalents, based on the compound (XLVI).

[0458] Examples of the solvent to be used include ethers such as dry THF, diethyl ether, dibutyl ether, etc. These solvents can be used alone or as mixtures with other solvents such as hydrocarbons (e.g., toluene, etc.), amines (e.g., triethylamine, etc.), etc.

[0459] The reaction temperature is room temperature to 150° C., preferably 40° C. to 100° C.

[0460] The reaction time is 10 minutes to 48 hours, preferably 30 minutes to 6 hours.

[0461] If necessary, as a reaction activating agent, a small amount of iodine, dibromoethane, ethyl bromide, etc., can be used. The amount thereof is 0.001 to 0.4 equivalent, preferably 0.005 to 0.2 equivalent.

[0462] The compound (XLVII) thus obtained can be used in the next step as the reaction mixture or the crude product.

[0463] [Route 16 (continued)]

[0464] wherein each symbol is as defined above.

[0465] The compound of the formula (XLVIII) can be prepared by reacting the compound (XLVII) with the compound (XII) or (XIII) in an appropriate solvent (alone or as a mixture).

[0466] The amount of the compound (XII) or (XIII) to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XLVII).

[0467] Examples of the solvent to be used is aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), triethylamine, mixed solvents thereof, etc.

[0468] The reaction temperature is −100° C. to 100° C., preferably −80° C. to 40° C.

[0469] The reaction time varies with the kind of compound, and is 0.5 to 80 hours.

[0470] The compound (XLVIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0471] [Route 16 (continued)]

[0472] wherein each symbol is as defined above.

[0473] The compound (XLIX) can be prepared by reacting the compound (XLVIII) with the compound (III) or a salt thereof in an appropriate solvent.

[0474] The amount of the compound (III) to be used is 1 to 4 equivalents, preferably 1 to 2.5 equivalents, based on the compound (XLVIII).

[0475] Examples of the salt of the compound (III) include mineral acid salts such as a hydrochloric acid salt, sulfuric acid salt, etc. When the salt is used, it is neutralized with a base for the reaction. Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, etc.), etc. The amount of the base to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the compound (III).

[0476] Examples of the solvent to be used is hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol, etc.), water, mixed solvents thereof, etc.

[0477] The reaction temperature is 0° C. to 150° C., preferably 20° C. to 100° C.

[0478] The reaction time is normally 15 minutes to 24 hours.

[0479] The compound (XLIX) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0480] [Route 16 (continued)]

[0481] wherein each symbol is as defined above.

[0482] The compound (XXXIX) can be obtained by deprotecting the protective group of the hydroxyl group of the compound (XLIX).

[0483] The hydroxyl group can be deprotected by a conventional method for deprotecting a protected hydroxyl group described in, e.g., T. W. Green, “Protective Groups in Organic Synthesis”, p. 1-113, John Willy & Sons (1981); C. B. Reese, “Protective Groups in Organic Chemistry”, J. F. McOmie (ed.), p.95-143, Plenum Press (1973).

[0484] For example, the deprotection can be carried out by treating the compound (XLIX) with an acid when the protective group of the hydroxyl group is alkyl (e.g., t-butyl, etc.), alkenyl (e.g., allyl, etc.), aralkyl (e.g., triphenylmethyl, etc.), trialkylsilyl (e.g., t-butyldimethylsilyl, triisopropylsilyl, etc.), alkyldiarylsilyl (e.g., t-butyldiphenylsilyl, etc.), triaralkylsilyl (e.g., tribenzylsilyl, etc.), alkoxyalkyl (e.g., methoxymethyl, l-ethoxyethyl, 1-methyl-1-methoxyethyl, etc.), alkoxyalkoxyalkyl (e.g., methoxyethoxymethyl, etc.), alkylthioalkyl (e.g., methylthiomethyl, etc.), tetrahydropyranyl (e.g., tetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, etc.), tetrahydrothiopyranyl (e.g., tetrahydrothiopyran-2-yl, etc.), tetrahydrofuranyl (e.g., tetrahydrofuran-2-yl, etc.), tetrahydrothiofuranyl (e.g., tetrahydrothiofuran-2-yl, etc.), aralkyloxyalkyl (e.g., benzyloxymethyl, etc.), etc.

[0485] In general, the acid to be used includes, for example, inorganic acids such as hydrohalogenic acids (e.g., hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.), hydrogen halides (e.g., hydrogen chloride, hydrogen bromide, hydrogen iodide, etc.), boric acid, phosphoric acid, sulfuric acid, etc., sulfonic acids (e.g., aliphatic sulfonic acids such as trifluoromethanesulfonic acid, etc., and aromatic sulfonic acids such as toluenesulfonic acid, etc.), carboxylic acids (e.g., acetic acid, trifluoroacetic acid, etc.), silica gel, Lewis acids [e.g., aluminium halides (e.g., aluminium chloride, etc.), zinc chloride, titanium tetrachloride, etc.], etc. One or more suitable acids can be selected from these acids to use them in the reaction.

[0486] The amount of the acid to be used is a trace amount to 1 equivalent. Alternatively, a carboxylic acid can be used as a solvent.

[0487] Examples of the solvent to be used is hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0488] The reaction temperature is −80° C. to 150° C., preferably −10° C. to 80° C.

[0489] The reaction time is 1 minute to 3 hours, preferably 5 minutes to 1 hour.

[0490] When the protective group is substituted silyl, for example, the deprotection can be carried out in basic conditions (e.g., sodium hydroxide/water-containing ethanol, etc.) or in the presence of fluoride ion (e.g., n-Bu₄N+F—, C₅H₅N+HF—, etc.).

[0491] The compound (XXXIX) thus obtained can be used in the next step as the reaction mixture or crude product.

[0492] If necessary, the product can be purified by a conventional method (e.g., column chromatography, recrystallization, etc.).

[0493] [Route 16 (continued)]

[0494] wherein each symbol is as defined above.

[0495] The compound (XXXIX) can be prepared by reacting the compound (XLVIII) with the compound (III) or a salt thereof in the presence of a base in an appropriate solvent. The amount of the compound (III) to be used is 1 to 4 equivalents, preferably 1 to 2.5 equivalents, based on the compound (XLVIII).

[0496] Examples of the salt of the compound (III) include mineral acid salts such as a hydrochloric acid salt, sulfuric acid salt, etc. When the salt is used, the salt is neutralized with a base for the reaction.

[0497] Examples of the base to be used include amines (pyridine, etc.), etc. The amount of the base to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the salt of the compound (III).

[0498] Examples of the solvent to be used is hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol, etc.), water, mixed solvents thereof, etc.

[0499] The reaction temperature is 0° C. to 150° C., preferably 20° C. to 200° C.

[0500] The reaction time is normally 15 minutes to 24 hours.

[0501] The compound (XXXIX) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., column chromatography, recrystallization, etc.).

[0502] [Route 16 (continued)]

[0503] wherein each symbol is as defined above.

[0504] The compound (L) can be prepared by reacting the compound (XLVIII) with hydroxylamine or a salt thereof in an appropriate solvent.

[0505] The amount of the hydroxylamine to be used is 1 to 4 equivalents, preferably 1 to 2.5 equivalents, based on the compound (XLVIII).

[0506] Examples of the salt of hydroxylamine include mineral acid salts such as a hydrochloric acid salt, sulfuric acid salt, etc. When the salt is used, it is neutralized with a base for the reaction. Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, etc.), etc. The amount of the base to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the salt of hydroxylamine.

[0507] Examples of the solvent to be used include hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol, etc.), water, mixed solvents thereof, etc.

[0508] The reaction temperature is 0° C. to 150° C., preferably 20° C. to 100° C.

[0509] The reaction time is normally 15 minutes to 24 hours.

[0510] The compound (L) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., column chromatography, recrystallization, etc.).

[0511] [Route 16 (continued)]

[0512] wherein each symbol is as defined above.

[0513] The compound of the formula (XLIX) can be prepared by reacting the compound (L) with the compound (XVII) in the presence of a base in an appropriate solvent (alone or as a mixture). The amount of the compound (XVII) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (L).

[0514] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.

[0515] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0516] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C.

[0517] The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0518] The compound (XLIX) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).

[0519] The compound of the formula (Il) of the present invention can be prepared according to the following Route 17.

[0520] [Route 17]

[0521] wherein V is oxygen, sulfur or N—R⁵, and R⁵ and the other symbols are as defined above.

[0522] The compound of the formula (Il) of the present invention can be prepared by reacting the compound (XXXVI) with the compound (LI) or a salt thereof (e.g., hydrochloric acid salt, hydrobromic acid salt, etc.) in the presence or absence of a base, or in the presence or absence of an acid, or in the presence or absence of a metal salt, in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to, e.g., T. W. Green, “Protective Groups in Organic Synthesis”, p. 109-151, John Willy & Sons (1981).

[0523] The amount of the compound (LI) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XXXVI).

[0524] Examples of the base to be used include amines (e.g., triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 6 equivalents, based on the compound (XXXVI).

[0525] Examples of the acid to be used include inorganic acids (e.g., hydrochloric acid, sulfuric acid, etc.) and sulfonic acids (e.g., p-toluenesulfonic acid, etc.). The amount of the acid to be used is 0.01 to 0.5 equivalent, preferably 0.02 to 0.2 equivalent, based on the compound (XXXVI).

[0526] Examples of the metal salt to be used include potassium carbonate, zinc acetate, etc. The amount of the metal salt to be used is 0.01 to 0.5 equivalent, preferably 0.02 to 0.2 equivalent, based on the compound (XXXVI).

[0527] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), alcohols (e.g., butanol, 2-methoxyethanol, ethylene glycol, glycerol, etc.), mixed solvents thereof, etc.

[0528] The reaction temperature is 20° C. to 200° C., preferably 50° C. to 160° C.

[0529] The reaction time varies with the kind of compound, and is 0.5 to 90 hours.

[0530] If necessary, the desired compound (Il) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).

[0531] The compound of the formula (Im) of the present invention can be prepared, for example, according to the following Route 18.

[0532] [Route 18]

[0533] wherein each symbol is as defined above.

[0534] The compound of the formula (LII) can be prepared by reacting the compound (XXXIXb) with a halogenating agent in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0535] Examples of the halogenating agent to be used include thionyl halides (e.g., thionyl chloride, thionyl bromide, etc.), phosphoryl halides (e.g., phosphoryl chloride, phosphoryl bromide, etc.), phosphorus halides (e.g., phosphorus pentachloride, phosphorus trichloride, phosphorus pentabromide, phosphorus tribromide, etc.), phosgene, oxalyl halides (e.g., oxalyl chloride, etc.), triphenylphosphine/carbon tetrachloride, triphenylphosphine/carbon tetrabromide, etc. The amount of the halogenating agent to be used is 1 equivalent or more.

[0536] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), nitriles (e.g., acetonitrile, etc.), mixed solvents thereof, etc.

[0537] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 120° C.

[0538] The reaction time varies with the kind of compound, and is 0.1 to 48 hours.

[0539] The compound (LII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., column chromatography, recrystallization, etc.).

[0540] [Route 18 (continued)]

[0541] wherein each symbol is as defined above.

[0542] The compound of the formula (Im) can be prepared by reacting the compound (LII) with the compound (IX) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).

[0543] The amount of the compound (IX) to be used in this reaction is 1 equivalent or more based on the compound (LII).

[0544] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more.

[0545] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.

[0546] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.

[0547] If necessary, the desired compound (Im) thus obtained can be purified by a conventional method (e.g., column chromatography, recrystallization, etc.).

[0548] The compound of the formula (I) of the present invention is effective against a wide variety of phytopathogenic fungi on crop plants (e.g., rice, wheat, barley, rye, corn, common millet, millet, buckwheat, soybean, redbean, peanut, etc.), fruit trees (e.g., citrus fruits, grape, apple, pear, peach, etc.), vegetables (e.g., cucumber, eggplant, tomato, pumpkin, kidney bean, etc.), etc., or seeds thereof. It is also effective against phytopathogenic fungi in soil. The compound of the present invention shows potent fungicidal activity particularly against Pyricularia oryzae, Rhizoctonia solani, Erysiphe graminis, Sphaerotheca fuliginea, Erysiphe cichoracearum, Phytophthora infestans, Pseudoperonospora cubensis, Peronospora manshurica, Plasmopara viticola, Botrytis cinerea of vegetables, grape, etc., Pythium aphanidermatum, Sclerotinia sclerotiorum of buckwheat, soybean, colza, etc., Corticium rolfsii of soybean, redbean, potato, peanut, etc., Pseudocercosporella herpotrichoides, of cereals, etc. Therefore, the compound (I) of the present invention is useful as fungicides, particularly as agricultural fungicides.

[0549] Application of the compound (I) of the present invention may be made to plants by any conventional procedure such as atomizing, scattering or spreading of the active compound. Application may also be made through treatment of seeds of plants, soil where plants grow, soil for seeding, paddy field or water for perfusion with the active compound. Application may be performed before or after the infection with phytopathogenic fungi on plants.

[0550] The compound can be used in a conventional formulation form suitable for agricultural fungicides such as solutions, wettable powders, emulsions, suspensions, concentrated liquid preparations, tablets, granules, aerosols, powders, pastes, dusts, etc.

[0551] Such formulation form can be prepared in a conventional manner by mixing at least one compound of the present invention with an appropriate solid or liquid carrier(s) and, if necessary, an appropriate adjuvant(s) (e.g., surfactants, spreaders, dispersants, stabilizers, etc.) for improving the dispersibility and other properties of the active ingredient.

[0552] Examples of the solid carriers or diluents include botanical materials (e.g., flour, tobacco stalk powder, soybean powder, walnut-shell powder, vegetable powder, saw dust, bran, bark powder, cellulose powder, vegetable extract residue, etc.), fibrous materials (e.g., paper, corrugated cardboard, old rags, etc.), artificial plastic powders, clays (e.g., kaolin, bentonite, fuller's earth, etc.), talc, other inorganic materials (e.g., pyrophyllite, sericite, pumice, sulfur powder, active carbon, etc.), chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.), etc.

[0553] Examples of the liquid carriers or diluents include water, alcohols (e.g., methanol, ethanol, etc.), ketones (e.g., acetone, ethyl methyl ketone, etc.), ethers (e.g., diethyl ether, dioxane, cellosolve, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, methylnaphthalene, etc.), aliphatic hydrocarbons (e.g., gasoline, kerosene, lamp oil, etc.), esters, nitriles, acid amides (e.g., dimethylformamide, dimethylacetamide, etc.), halogenated hydrocarbons (e.g., dichloroethane, carbon tetrachloride, etc.), etc.

[0554] Examples of the surfactants include alkyl sulfates, alkyl sulfonates, alkylaryl sulfonates, polyethylene glycol ethers, polyhydric alcohol esters, etc.

[0555] Examples of the spreaders or dispersants include casein, gelatin, starch powder, carboxymethyl cellulose, gum arabic, alginic acid, lignin, bentonite, molasses, polyvinyl alcohol, pine oil, agar, etc.

[0556] Examples of the stabilizers include PAP (a mixture of isopropylphosphate), tricresyl phosphate (TCP), tolu oil, epoxidized oil, surfactants, fatty acids and their esters, etc.

[0557] The composition of the present invention may contain other fungicides, insecticides, herbicides or fertilizers in addition to the above ingredients.

[0558] In general, the above composition contains at least one compound of the formula (I) of the present invention in a concentration of 1 to 95% by weight, preferably 2.0 to 80% by weight. The composition can be used as such or in a diluted form. About 1.0 g to 5 kg/hectare, preferably about 10 g to 1000 g/hectare, of the compound of the present invention is used in a concentration of normally about 1 to 5,000 ppm, preferably about 10 to 1,000 ppm.

EXAMPLES

[0559] The following Examples and Test Examples further illustrate the present invention in detail, but are not to be construed to limit the scope thereof. The 1H-NMR (CDCl₃) data in Examples were determined at 270 MHz in CDCl₃ using tetramethylsilane as an internal standard and indicated in δ values (ppm). The coupling constants (J) are indicated in Hz. In the data, s is a singlet, d is a doublet, t is a triplet, q is a quartet, m is a multiplet, brs is a broad singlet.

Example 1 Synthesis of α-ethoxyimino-2-phenoxymethylbenzyl Chloride

[0560] Dichloroethane (50 ml), thionyl chloride (6.54 g, 0.055 mol) and dimethylformamide (0.25 ml) were added to 2-phenoxymethylbenzoic acid (11.41 g, 0.05 mol), and the mixture was stirred at 80° C. for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was dissolved in dichloromethane (25 ml). The solution was added to a mixture of ethoxyamine hydrochloride (5.85 g, 0.06 mol), pyridine (9.89 g, 0.125 mol) and dry dichloromethane (50 ml) under ice-cooling over 20 minutes, and then the resulting mixture was stirred at room temperature for 2 hours. After completion of the reaction, water (200 ml) was added, adjusted to pH<2 with conc. hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Acetonitrile (150 ml), triphenylphosphine (20.98 g, 0.08 mol) and carbon tetrachloride (24.61 g, 0.16 mol) were added to the residue, and the mixture was stirred under reflux for 1.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give α-ethoxyimino-2-phenoxymethylbenzyl chloride (13.51 g, 93.2%) as a colorless oil.

[0561]¹H-NMR (CDCl₃) δ ppm: 3.14 (3H, t, J=6.7), 4.27 (2H, q, J=6.7), 5.28 (2H, s), 6.93-7.70 (9H, m).

Synthesis of 1-(α-ethoxyimino-2-phenoxymethylbenzyl)-1H-1,2,4-triazole

[0562] Dimethylformamide (3 ml) and 60% sodium hydride (0.12 g, 3 mmol) were added to 1H-1,2,4-triazole (0.20 g, 3 mmol), and the mixture was stirred at room temperature for 10 minutes. Then α-ethoxyimno-2-phenoxymethylbenzyl chloride (0.43 g, 1.5 mmol) was added, and the mixture was stirred at 120° C. for 5 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 1-(α-ethoxyimino-2-phenoxymethylbenzyl)-1H-1,2,4-triazole (0.42 g, 86.9%) as colorless crystals. mp. 78.5-80.5° C.

[0563]¹H-NMR (CDCl₃) δ ppm: 1.35 (3H, t, J=6.7), 4.30 (2H, q, J=6.7), 4.93 (2H, s), 6.76-7.55 (9H, m), 7.94 (1H, s), 9.14 (1H, s).

Example 2 Synthesis of 2-chloromethyl-α-methoxyiminobenzyl Chloride

[0564] 2-Chloromethylbenzoyl chloride (18.90 g, 0.1 mol) was dissolved in dichloromethane (50 ml). The solution was added to a mixture of methoxyamine hydrochloride (12.53 g, 0.15 mol), pyridine (19.78 g, 0.25 mol) and dry dichloromethane (150 ml) under ice-cooling over 1 hour, and then the resulting mixture was stirred at 0° C. for 2 hours. After completion of the reaction, water (300 ml) was added, adjusted to pH<2 with conc. hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (200 ml), and phosphorus pentachloride (20.82 g, 0.1 mol) was added under ice-cooling over 5 minutes. The mixture was stirred at 0° C. for 1 hour. After completion of the reaction, saturated aqueous sodium bicarbonate solution (400 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-chloromethyl-α-methoxyiminobenzyl chloride (18.15 g, 83.2%) as a colorless oil.

[0565]¹H-NMR (CDCl₃) δ ppm: 4.12 (3H, s), 4.83 (2H, s), 7.40-7.62 (4H, m).

Synthesis of 2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl Chloride

[0566] 3-Chlorophenol (3.09 g, 0.024 mol), dimethylformamide (20 ml) and potassium carbonate (4.15 g, 0.03 mol) were added to 2-chloromethyl-α-methoxyiminobenzyl chloride -(4.36 g, 0.02 mol), and the mixture was stirred at room temperature for 4 days. After completion of the reaction, ether (250 ml) was added, and the mixture was washed with brine (200 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl chloride (5.66 g, 91.2%) as a colorless oil.

[0567]¹H-NMR (CDCl₃) δ ppm: 4.02 (3H, s), 5.25 (2H, s), 6.80-7.70 (8H, m).

Synthesis of 1-[2-(3-chlorophenoxymethyl)-α-methoxy-iminobenzyl]imidazole

[0568] Dimethylformamide (3 ml) and 60% sodium hydride (0.16 g, 3.9 mmol) were added to imidazole (0.27 g, 3.9 mmol), and the mixture was stirred at room temperature for 10 minutes. Then, 2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl chloride (0.40 g, 1.3 mmol) was added, and the mixture was stirred at 110° C. for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 1-[2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl]imidazole (0.29 g, 65.3%) as colorless crystals. mp. 96.5-97.5° C.

[0569]¹H-NMR (CDCl₃) δ ppm: 3.97 (3H, s), 5.00 (2H, s), 6.63-7.60 (10H, m), 7.98 (1H, s).

[0570] According to the same manner as that of the synthesis of the intermediate in Example 1 or 2, various compounds of the formula (V) of the present invention, which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds obtained in Examples 1 and 2 are also listed.

No R¹ R² n Physical data V-1 C₆H₅ Me 0 ¹H-NMR(CDCl₃) δ ppm:4.02(3H, s), 6.94-7.55(9H, m) V-2 C₆H₅ Me 1 ¹H-NMR(CDCl₃) δ ppm:4.02(3H, s), 5.28(2H, s), 6.93-7.69(9H, m) V-3 C₆H₅ Et 1 ¹H-NMR(CDCl₃) δ ppm:1.34(3H, t, J=6.7), 4.27(2H, q, J=6.7), 5.28(2H, s), 6.93-7.70(9H, m) V-4 C₆H₅ Allyl 1 ¹H-NMR(CDCl₃) δ ppm:4.69-4.72(2H, m), 5.24-5.38(2H, m), 5.25(2H, s), 5.94-6.08(1H, m), 6.93-7.71(9H, m) V-5 2-Cl—C₆H₄ Me 1 ¹H-NMR(CDCl₃) δ ppm:4.07(3H, s), 5.37(2H, s), 6.88- 7.79(8H, m) V-6 3-Cl—C₆H₄ Me 1 ¹H-NMR(CDCl₃) δ ppm:4.02(3H, s), 5.25(2H, s), 6.80-7.70(8H, m) V-7 4-Cl—C₆H₄ Me 1 ¹H-NMR(CDCl₃) δ ppm:4.01(3H, s), 5.24(2H, s), 6.85-7.70(8H, m) V-8 2-Me—C₆H₄ Me 1 ¹H-NMR(CDCl₃) δ ppm:2.30(3H, s), 4.03(3H, s), 5.23(2H, s), 6.80-7.70(8H, m) V-9 4-Me—C₆H₄ Me 1 ¹H-NMR(CDCl₃) δ ppm:2.28(3H, s), 4.03(3H, s), 5.25(2H, s), 6.84(2H, d, J=8.5), 7.08(2H, d, J=8.5) V-10 2-Et—C₆H₄ Me 1 ¹H-NMR(CDCl₃) δ ppm:1.24(3H, t, J=7.3), 2.73(2H, q, J=7.3), 4.05(3H, s), 5.29(2H, s), 6.81-7.70(8H, m) V-11 2,5-Me₂—C₆H₃ Me 1 ¹H-NMR(CDCl₃) δ ppm:2.25(3H, s), 2.30(3H, s), 4.05(3H, s), 5.26(2H, s), 6.65—7.70(7H, m) V-12 2,6-Me₂—C₆H₃ Me 1 ¹H-NMR(CDCl₃) δ ppm:2.28(6h, s), 4.02(3H, s), 5.02(2H, s), 6.93-7.62(6H, m), 7.90(1H, d, J=7.9) V-13 2-Cl-pyridin-3-yl Me 1 mp 65-66° C.

Example 3 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl Ketone

[0571] THF (2 ml) and bromoethane (0.1 ml) were added to magnesium (0.49 g, 0.02 mol) in a stream of nitrogen, and the mixture was stirred at 50° C. for 10 minutes. Then, a mixture of 1-bromo-2-(2,5-dimethylphenoxymethyl)benzene (2.91 g, 0.01 mol) and THF (8 ml) was added at 50 to 60° C. over 30 minutes, and the mixture was stirred at 50 to 60° C. for 1 hour. After completion of the reaction, the reaction mixture was added to a mixture of 3-methylisoxazol-5-carbonyl chloride (1.45 g, 0.01 mol) and THF (15 ml) at −70 to −60° C. over 15 minutes, and then the mixture was stirred at −70 to −60° C. for 0.5 hours. After completion of the reaction, saturated aqueous ammonium chloride solution (150 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone (0.56 g, 17.4%) as colorless crystals. mp. 106-108° C.

[0572]¹H-NMR (CDCl₃) δ ppm: 2.13 (3H, s), 2.28 (3H, s), 2.38 (3H, s), 5.28 (2H, s), 6.66 (1H, s), 6.67 (1H, d, J=6.7), 6.72 (1H, s), 7.00 (1H, d, J=7.9), 7.46-7.83 (4H, m).

Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl Ketone O-methyloxime

[0573] n-Propanol (2 ml) and methoxyamine hydrochloride (0.25 g, 3 mmol) were added to 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone (0.33 g, 1 mmol), and the mixture was stirred under reflux for 15 hours. After completion of the reaction, water (200 ml) was added, the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.18 g, 51.4%, as colorless crystals) and isomer B (0.15 g, 42.8%, as colorless crystals) of 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone O-methyloxime. One of the isomers A and B is the E-isomer and the other is Z-isomer.

[0574] Isomer A: mp. 113-114° C.

[0575]¹H-NMR (CDCl₃) δ ppm: 2.11 (3H, s), 2.25 (3H, s), 2.33 (3H, s), 4.12 (3H, s), 4.98 (2H, s), 6.51 (1H, s), 6.64 (1H, d, J=7.3), 6.91 (1H, s), 6.97 (1H, d, J=7.3), 7.38-7.62 (4H, m).

[0576] Isomer B: mp. 107-108° C.

[0577]¹H-NMR (CDCl₃) δ ppm: 2.13 (3H, s), 2.24 (3H, s), 2.26 (3H, s), 4.04 (3H, s), 4.93 (2H, s), 5.99 (1H, s), 6.53 (1H, s), 6.65 (1H, d, J=7.9), 6.99 (1H, d, J=7.3), 7.21-7.52 (3H, m), 7.68 (1H, d, J=7.9).

Example 4 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl Ketone

[0578] THF (2 ml) and bromoethane (0.1 ml) were added to magnesium (0.49 g, 0.02 mol) in a stream of nitrogen, and the mixture was stirred at 50° C. for 10 minutes. Then, a mixture of 1-bromo-2-(2,5-dimethylphenoxymethyl)benzene (2.91 g, 0.01 mol) and THF (8 ml) was added at 50 to 60° C. over 30 minutes, and the mixture was stirred at 50 to 60° C. for 1 hour. After completion of the reaction, the reaction mixture was added to a mixture of 3-cyanoisoxazole (1.45 g, 0.015 mol) and THF (15 ml) at 20° C. or lower over 15 minutes, and then the mixture was stirred at room temperature for 2 hours. After completion of the reaction, 2N sulfuric acid (200 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl ketone (0.20 g, 6.3%) as colorless crystals. mp. 90.5-92° C.

[0579]¹H-NMR (CDCl₃) δ ppm: 2.16 (3H, s), 2.29 (3H, s), 5.32 (2H, s), 6.66 (1H, s), 6.67 (1H, d, J=6.7), 6.86 (1H, d, J=1.2), 7.00 (1H, d, J=7.3), 7.47 (1H, t, J=7.3), 7.60-8.03 (3H, m), 8.50 (1H, d, J=1.8).

Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl Ketone O-methyloxime

[0580] n-Propanol (2 ml) and methoxyamine hydrochloride (0.50 g, 6 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-phenyl isoxazol-3-yl ketone (0.64 g, 2 mmol), and the mixture was stirred under reflux for 17 hours. After completion of the reaction, water (100 ml) was added, the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (benzene/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl ketone O-methyloxime (a mixture of isomers A/B) (0.55 g, 81.8%) as colorless crystals. mp. 104-108° C.

[0581]¹H-NMR (CDCl₃) δ ppm: 2.13 (2.15) (3H, s), 2.23 (2.25) (3H, s), 4.01 (4.08) (3H, s), 4.95 (5.01) (2H, s), 6.52-7.00 (4H, m), 7.29-7.64 (4H, m), 8.39 (8.45) (1H, d, J=1.8).

Example 5 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl Ketone

[0582] Dichloroethane (20 ml), thionyl chloride (1.31 g, 0.011 mol) and dimethylformamide (0.1 ml) were added to 2-(2,5-dimethylphenoxymethyl)benzoic acid (2.56 g, 0.01 mol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to give crude 2-(2,5-dimethylphenoxymethyl)benzoyl chloride. 1.6M n-butyllithium/n-hexane solution (6.25 ml, 0.01 mol) was added to a mixture of 1-methylpyrazole (0.99 g, 0.012 mol) and THF (10 ml) at −70 to −60° C. over 15 minutes, and then the mixture was stirred at −70° C. to room temperature for 1 hour. The reaction mixture was cooled to −70° C., and a solution of the crude 2-(2,5-dimethylphenoxymethyl)benzoyl chloride in THF (10 ml) was added, and the mixture was stirred at −70° C. for 1 hour. After completion of the reaction, 1N hydrochloric acid (100 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl ketone (0.50 g, 15.6%) as colorless crystals.

[0583] mp. 88-89° C.

[0584]¹H-NMR (CDCl₃) δ ppm: 2.04 (3H, s), 2.28 (3H, s), 4.22 (3H, s), 5.23 (2H, s), 6.50 (1H, d, J=2.4), 6.65 (1H, s), 6.66 (1H, d, J=6.7), 6.97 (1H, d, J=7.3), 7.38-7.76 (4H, m).

Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl Ketone O-ethyloxime

[0585] n-Propanol (2 ml) and ethoxyamine hydrochloride (0.18 g, 1.8 mmol) were added to 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl ketone (0.20 g, 0.6 mmol), and the mixture was stirred under reflux for 3 days. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.11 g, 50.4%, as colorless crystals) and isomer B (0.10 g, 45.9%, as colorless crystals) of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl ketone O-ethyloxime.

[0586] Isomer A: mp. 74-76° C.

[0587]¹H-NMR (CDCl₃) δ ppm: 1.30 (3H, t, J=7.3), 2.13 (3H, s), 2.23 (3H, s), 4.13 (3H, s), 4.24 (2H, q, J=7.3), 4.95 (2H, s), 5.92 (1H, d, J=2.4), 6.51 (1H, s), 6.64 (1H, d, J=7.9), 6.99 (1H, d, J=7.3), 7.17-7.64 (5H, m).

[0588] Isomer B: mp. 84-86° C.

[0589]¹H-NMR (CDCl₃) δ ppm: 1.33 (3H, t, J=6.7), 2.23 (3H, s), 2.29 (3H, s), 3.68 (3H, s), 4.29 (2H, q, J=6.7), 5.14 (2H, s), 6.30 (1H, d, J=1.8), 6.58 (1H, s), 6.68 (1H, d, J=7.3), 7.03 (1H, d, J=7.3), 7.16-7.47 (3H, m), 7.52 (1H, d, J=1.8), 7.73 (1H, d, J=7.9).

[0590] According to the same manner as that of the syntheses of the intermediates in Examples 3 to 5, various compounds of the formula (XIV) of the present invention, which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds obtained in Examples 3 to 5 are also listed.

No R¹ R³ n Physical data XIV-1 C₆H₅ 1-Me-imidazol- 0 ¹H-NMR(CDCl₃) δ ppm:3.94(3H, s), 2-yl 6.92-7.30(7H, m), 7.43(H, td, J=8.6, 1.8), 7.64(1H, dd, J=7.9, 1.8) XIV-2 2,5-Me_(2pl —C) ₆H₃ 1-Me-imidazol- 1 ¹H-NMR(CDCl₃) δ ppm:2.07(3H, s), 2-yl 2.26(3H, s), 4.01(3H, s), 5.23(2H, s), 6.00(1H, s), 6.64(1H, d, J=7.3), 6.97(1H, d, J=7.3), 7.05(1H, s), 7.19(1H, s), 7.40-7.83(4H, m) XIV-3 C₆H₅ Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm:5.34(2H, s), 6.85-7.28(6H, m), 7.46(1H, t, J=7.3), 7.61(1H, td, J=7.9, 1.2), 7.74(1H, d, J=7.9), 7.99(1H, dd, J=7.3, 1.2), 8.50(1H, dd, J=1.2) XIV-4 2-Me—C₆H₄ Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm:2.21(3H,s), 5.34(2H, s), 6.80-7.14(5H, m), 7.44- 8.02(4H, m), 8.49(1H, d, J=1.2) XIV-5 2,5-Me₂—C₆H₃ Isoxazol-3-yl 1 mp 90.5-92° C. XIV-6 C₆H₅ 5-Me-isoxazol- 1 ¹H-NMR(CDCl₃) δ ppm:2.49(3H, s), 3-yl 5.34(2H, s), 6.46(1H, d, J=1.2), 6.88- 7.99(9H, m) XIV-7 2,5-Me₂—C₆H₃ 5 Me- 1 ¹H-NMR(CDCl₃) δ ppm:2.17(3H, s), isoxazol-3-yl 2.28(3H, s), 2.49(3H, s), 5.32(2H, s), 6.46(1H, s), 6.66-7.02(3H, m), 7.42- 8.00(4H, m) XIV-8 2-Me—C₆H₄ 3-Me- 1 ¹H-NMR(CDCl₃) δ ppm:2.18(3H, s), isoxazol-5-yl 2.38(3H, s), 5.30(2H, s), 6.71(1H, s), 6.81-7.80(8H, m) XIV-9 2,5-Me₂—C₆H₃ 3-Me- 1 mp 106-108° C. isoxazol-5-yl XIV-10 2,5-Me₂—C₆H₃ 2-Isoxazolin- 1 ¹H-NMR(CDCl₃) δ ppm:2.17(3H, s), 3-yl 2.31(3H, s), 3.20(2H, t, J=11.0), 4.42(2H, t, J=11.0), 5.20(2H, s), 6.68- 7.84(7H, m) XIV-11 2,5-Me₂—C₆H₃ 5,5-Me₂-2- 1 ¹H-NMR(CDCl₃) δ ppm:1.35(6H, s), isoxazolin-3-yl 2.16(3H, s), 2.30(3H, s), 2.96(2H, s), 5.22(2H, s), 6.67-7.80(7H, m) XIV-12 2,5-Me₂—C₆H₃ 1-Me- 1 mp 88-89° C. pyrazol-5-yl XIV-13 2,5-Me₂—C₆H₃ 2-Furyl 1 ¹H-NMR(CDCl₃) δ ppm:2.10(3H, s), 2.26(3H, s), 5.25(2H, s), 6.55- 6.67(3H, m), 6.97(1H, d, J=7.3), 7.06(1H, d, J=3.7), 7.39-7.80(5H, m) XIV-14 2,5-Me₂—C₆H₃ Thiazol-2-yl 1 ¹H-NMR(CDCl₃) δ ppm:2.11(3H, s), 2.27(3H, s), 5.30(2H, s), 6.64(1H, s), 6.65(1H, d, J=2.5), 6.98(1H, d, J=7.9), 7.45-8.10(6H, m) XIV-15 2,5-Me₂—C₆H₃ 3-Me- 1 ¹H-NMR(CDCL₃) δ ppm:2.07(3H, s), isothiazol-5-yl 2.27(3H, s), 2.53(3H, s), 5.25(2H, s), 6.60-7.82(8H, m) XIV-16 4-Cl-2-Me—C₆H₃ 5-Me- 1 mp 103-104° C. isoxazol-3-yl XIV-17 3-Me-C₆H₄ Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm:2.30(3H, s), 5.32(2H, s), 6.66-6.77(3H, m), 6.87(1H, s), 7.12(1H, t, J=7.3), 7.46- 7.76(3H, m), 8.00(1H, d, J=7.9), 8.50(1H, s) XIV-18 4-Me-C₆H₄ Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm:2.26(3H, s), 5.30(2H, s), 6.77(2H, d, J=8.6), 6.86(1H, d, J=1.8), 7.04(2H, d, J=8.6), 7.45-7.98(4H, m), 8.50(1H, d, J=1.8) XIV-19 2-Cl-C₆H₄ Isoxazol-3-yl 1 mp 92.0-93.0° C. XIV-20 3-Cl-C₆H₄ Isoxazol-3-yl 1 mp 75.0-76.0° C. XIV-21 4-Cl-C₆H₄ Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm:5.32(2H, s), 6.80-6.83(2H, m), 6.86(1 H, d, J=1.8), 7.19-7.22(2H, m), 7.45-8.02(4H, m), 8.52(1H, d, J=1.2) XIV-22 3-CF₃—C₆H₄ Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm:5.38(2H, s), 6.87(1H, d, J=1.8), 7.04-7.75(7H, m), 8.04(1H, d, J=7.9), 8.52(1H, d, J=1.8) XIV-23 4-Cl-2-Me—C₆H₃ Isoxazol-3-yl 1 mp 107.0-108.0° C. XIV-24 2-Me—C₆H₄ 5-Me- 1 mp 77.5-78.5° C. isoxazol-3-yl XIV-25 3-Me—C₆H₄ 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm:2.30(3H, s), isoxazol-3-yl 2.49(3H, s), 5.32(2H, s), 6.47(1H, d, J=1.2), 6.67-6.85(3H, m), 7.12(1H, t, J=7.3), 7.41-7.98(4H, m) XIV-26 4-Me—C₆H₄ 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm:2.26(3H, s), isoxazol-3-yl 1 2.49(3H, s), 5.30(2H, s), 6.46(1H, s), 6.77-6.80(2H, m), 7.05(2H, d, J=7.9), 7.40-7.97(4H, m) XIV-27 2-Cl—C₆H₄ 5-Me- 1 mp 93.5-94.5° C. isoxazol-3-yl XIV-28 3-CL—C₆H₄ 5-Me- 1 mp 72.0-73.0° C. isoxazol-3-yl XIV-29 4-Cl—C₆H₄ 5-Me- 1 mp 95.0-96.0° C. isoxazol-3-yl XIV-30 3-CF₃—C₆H₄ 5-Me- 1 mp 58.5-59.5° C. isoxazol-3-yl XIV-31 4-Ph—C₆H₄ 5-Me- 1 mp 116.5-117.5° C. isoxazol-3-yl XIV-32 2-Me—C₆H₄ Isoxazol-5-yl 1 mp 67.5-68.5° C. XIV-33 2,5-Me₂—C₆H₃ Isoxazol-5-yl 1 mp 103.5-105.0° C. XIV-34 4-Cl-2-Me—C₆H₃ Isoxazol-5-yl 1 mp 109.5-111.0° C. XIV-35 C₆H₅ 3-Me- 0 ¹H-NMR(CDCl₃) δ ppm:2.30(3H, s), isoxazol-5-yl 6.76(1H, s), 6.91(1H, d, J=7.3), 6.99- 7.51(7H, m), 7.63(1H, dd, J=7.3, 1.8) XIV-36 3-Me—C₆H₄ 3-Me- 1 mp 68.0-69.0° C. isoxazol-5-yl XIV-37 2-Cl—C₆H₄ 3-Me- 1 mp 104.0-105.0° C. isoxazol-5-yl XIV-38 3-Cl—C₆H₄ 3-Me- 1 mp 92.5-93.5° C. isoxazol-5-yl XIV-39 3-CF₃—C₆H₄ 3-Me- 1 mp 80.5-81.5° C. isoxazol-5-yl XIV-40 4-Cl-2-Me—C₆H₃ 3-Me- 1 mp 125.5-126.5° C. isoxazol-5-yl XIV-41 4-Ph—C₆H₄ 3-Me- 1 mp 127.0-128.0° C. isoxazol-5-yl XIV-42 C₆H₅ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:4.01(3H, s), imidazol-2-yl 5.24(2H, s), 6.80-6.83(2H, m), 6.91(1H, t, J=7.3), 7.04(1H, s), 7.18- 7.81(7H, m) XIV-43 2-Me—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:2.13(3h, s), imidazol-2-yl 4.01(3H, s), 5.25(2H, s), 6.78-6.85(2H, m), 7.05(1H, s), 7.10(1H, d, J=7.3), 7.18(1H, s), 7.39-7.83(4H, m) XIV-44 3-Me—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:2.28(3H, s), imidazol-2-yl 4.01(3H, s), 5.21(2H, s), 6.59-6.74(3H, m), 7.04(1H, s), 7.09(1H, t, J=7.9), 7.18(1H, s), 7.39-7.80(4H, m) XIV-45 4-Me—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:2.25(3H, s), imidazol-2-yl 4.02(3H, s), 5.20(2H, s), 6.69-6.72(2H, m), 6.99-7.02(2H, m), 7.05(1H, s), 7.18(1H, s), 7.38-7.79(4H, m) XIV-46 2-Cl—C₆H₄ 1-Me- 1 mp 87.0-88.0° C. imidazol-2-yl XIV-47 3-Cl—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:4.03(3h, S), imidazol-2-yl 5.23(2H, s), 6.70(1H, dd, J=8.6, 1.8), 6.82(1H, t, J=1.8), 6.90(1H, dd, J=7.3, 1.2), 7.06(1H, s), 7.13(1H, t, J=7.9), 7.19(1H, d, J=1.2), 7.40-7.81(3H, m) XIV-48 4-Cl—c₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:4.03(3H, s), imidazol-2-yl 5.22(2H, s), 6.73-6.78(2H, m), 7.06(1H, s), 7.13-7.59(6H, m), 7.80(1H, dd, J=7.3, 1.2) XIV-49 2,4-Cl₂—C₆H₃ 1-Me- 1 mp 141.0-142.0°0 C. imidazol-2-yl XIV-50 3,4-Cl₂—C₆H₃ 1-Me- 1 mp 78.0-79.0° C. imidazol-2-yl XIV-51 4-Cl-2-Me—C₆H₃ 1-Me- 1 mp 101.0-102.0° C. imidazol-2-yl XIV-52 3-CF₃—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:4.01(3H, s), imidazol-2-yl 5.28(2H, s), 6,97-7.61(9H, m), 7.80(1H, dd, J=7.9, 1.8) XIV-53 2-MeO—C₆H₄ 1-Me- 1 mp 88.0-89.0° C. imidazol-2-yl XIV-54 3-MeO—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:3.74(3H, s), imidazol-2-yl 4.02(3H, s), 5.21(2H, s), 6.38-6.50(3H, m), 7.05(1H, s), 7.11(1H, t, J=7.9), 7.18(1H, s), 7.42-7.79(4H, m) XIV-55 4-F—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:4.03(3H, s), imidazol-2-yl 5.21(2H, s), 6.72-6.95(4H, m), 7.06(1H, s), 7.18(1H, d, J=1.2), 7.42- 7.80(4H, m) XIV-56 3-i-Pr—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:1.20(6H, d, imidazol-2-yl J=7.3), 2.83(1H, sept, J=7.3), 4.00(3H, s), 5.21(2H, s), 6.60-6.80(3H, m), 7.03(1H, s), 7.11-7.79(6H, m) XIV-57 4-Ph—C₆H₄ 1-Me- 1 ¹H-NMR(CDCl₃) δ ppm:4.03(3H, s), imidazol-2-yl 5.28(2H, s), 6.87-6.90(2H, m), 7.06(1H, s), 7.19(1H, s), 7.28- 7.84(11H, m) XIV-58 C₆H₅ 3,5-Me₂- 1 ¹H-NMR(CDCl₃) δ ppm:2.17(3H, s), isoxazol-4-yl 2.25(3H, s), 5.19(2H, s), 6.78—6.82(2H, m), 6.93(1H, t, J=7.3), 7.21-7.67(6H, m) XIV-59 2,5-Me₂—C₆H₃ 3,5-Me₂- 1 mp 109.0-110.5° C. isoxazol-4-yl XIV-60 2-Me—C₆H₃ 3-Me-2-isoxazolin- 1 ¹H-NMR(CDCl₃) δ ppm:2.02(3H, s), 5-yl 2.32(3H, s), 3.08(1H, m), 3.53- 3.62(1H, m), 5.33-5.46(2H, m), 5.69(1H, dd, J=11.6, 6.7), 6.88(1H, s), 6.91(1H, s), 7.15(1H, t, J=8.5), 7.43- 8.01(4H, m) XIV-61 2,5-Me₂—C₆H₃ 3-Me-2-isoxazolin- 1 mp 88.0-90.0° C. 5-yl XIV-62 C₆H₅ 4-Me-1,2,3- 1 ¹H-NMR(CDCl₃) δ ppm 2.77(3H, s), thiadiazol-5-yl 5.26(2H, s), 6.76(1H, s), 6.79(1H, d, J=1.2), 6.94(1H, t, J=7.3), 7.21- 7.74(6H, m) XIV-63 2,5-Me₂—C₆H₃ 4-Me-1,2,3- 1 mp 98.5-99.5° C. thiadiazol-5-yl XIV-64 2-Me—C₆H₄ 5-Me-2-isoxazolin- 1 3-yl XIV-65 C₆H₅ 5-Me-2-isoxazolin- 1 3-yl XIV-66 4-Cl—C₆H₄ 5-Me-2-isoxazolin- 1 3-yl XIV-67 3-CF₃—C₆H₄ 5-Me-2-isoxazolin- 1 3-yl XIV-68 4-Cl-2-Me—C₆H₃ 5-Me-2-isoxazolin- 1 3-yl XIV-69 4-Cl—C₆H₄ 2-Isoxazolin-3-yl 1 XIV-70 3-CF₃—C₆H₄ 2-Isoxazolin-3-yl 1 XIV-71 4-Cl-2-Me—C₆H₃ 2-Isoxazolin-3-yl 1 XIV-72 2-Me—C₆H₄ 2-Isoxazolin-3-yl 1 XIV-73 C₆H₅ 2-Isoxazolin-3-yl 0 XIV-74 C₆H₅ Isoxazol-3-yl 0

Example 6 Synthesis of 2-(4-chlorophenoxymethyl)phenyl 1-methyl-1H-1,2,4-triazol-5-yl Ketone O-methyloxime

[0591] Dimethylformamide dimethylacetal (0.53 g, 4.5 mmol) was added to 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetamide (0.48 g, 1.5 mmol), and the mixture was stirred under reduced pressure (ca. 40 mmHg) at 60° C. for 0.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and a mixture of methylhydrazine (0.08 g, 1.8 mmol) and acetic acid (3 ml) was added to the residue. The mixture was stirred at 90° C. for 1 hour. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (100 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 1-methyl-1H-1,2,4-triazol-5-yl ketone O-methyloxime (0.31 g, 57.9%) as colorless crystals.

[0592] mp. 113-114° C.

[0593]¹H-NMR (CDCl₃) δ ppm: 4.01 (3H, s), 4.08 (3H, s), 4.91 (2H, s), 6.67-6.70 (2H, m), 7.15-7.18 (2H, m), 7.26-7.54 (4H, m), 7.83 (1H, s).

[0594] Example 7

Synthesis of 2-(4-chlorophenoxymethyl)-N-hydroxyaminomethylene-α-methoxyiminophenylacetamide

[0595] Dimethylformamide dimethylacetal (0.53 g, 4.5 mmol) was added to 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetamide (0.48 g, 1.5 mmol), and the mixture was stirred under reduced pressure (ca. 40 mmHg) at 60° C. for 0.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and a mixture of aqueous 50% hydroxylamine solution (0.20 g, 2 mmol) and acetic acid (3 ml) was added to the residue under ice-cooling. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, ethyl acetate (150 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (100 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)-N-hydroxyaminomethylene-α-methoxyiminophenylacetamide (0.41 g, 75.6%) as colorless crystals.

[0596] mp. 185-186° C. (decomposition)

[0597]¹H-NMR (CDCl₃) δ ppm: 4.00 (3H, s), 4.93 (2H, s), 6.76-6.80 (2H, m), 6.86 (1H, d, J=8.5), 7.18-7.22 (2H, m), 7.37-7.52 (3H, m), 7.70 (1H, d, J=10.4), 9.50 (1H, d, J=9.8).

Synthesis of 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-5-yl Ketone O-methyloxime

[0598] Dioxane (2 ml) and acetic acid (1.5 ml) were added to 2-(4-chlorophenoxymethyl)-N-hydroxyaminomethylene-α-methoxyiminophenylacetamide (0.36 g, 1 mmol), and the mixture was stirred at 120° C. for 4 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (100 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.14 g, 40.8%) as colorless crystals.

[0599] mp. 96-97.5° C.

[0600]¹H-NMR (CDCl₃) δ ppm: 4.09 (3H, s), 4.94 (2H, s), 6.66-6.70 (2H, m), 7.14-7.17 (2H, m), 7.28-7.60 (4H, m), 8.44 (1H, s).

Example 8 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl Ketone O-methyloxime

[0601] Dichloroethane (5 ml), thionyl chloride (0.65 g, 5.5 mmol) and dimethylformamide (0.05 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetic acid (1.57 g, 5 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, pyridine (3 ml) and 1-hydroxyimino-1-propylamine (0.88 g, 10 mmol) were added to the residue, and the mixture was stirred under reflux for 0.5 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with IN hydrochloric acid (150 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.63 g, 34.5%) as colorless crystals.

[0602] mp. 111.5-112.5° C.

[0603]¹H-NMR (CDCl₃) δ ppm: 1.30 (3H, t, J=7.3), 2.09 (3H, s), 2.25 (3H, s), 2.77 (2H, q, J=7.3), 4.11 (3H, s), 4.95 (2H, s), 6.54 (1H, s), 6.65 (1H, d, J=7.9), 6.98 (1H, d, J=7.3), 7.27-7.66 (4H, m).

Example 9 Synthesis of 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetohydrazide

[0604] Methanol (10 ml), THF (10 ml) and hydrazine monohydrate (1.68 g, 0.03 mol) were added to methyl 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetate (3.27 g, 0.01 mol), and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, water (200 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetohydrazide (2.93 g, 89.6%) as colorless crystals.

[0605] mp. 124.5-126° C.

[0606]¹H-NMR (CDCl₃) δ ppm: 2.18 (3H, s), 2.29 (3H, s), 3.88 (2H, d, J=4.3), 3.96 (3H, s), 4.92 (2H, s), 6.61 (1H, s), 6.67 (1H, d, J=7.3), 7.01 (1H, d, J=7.3), 7.21-7.59 (4H, m), 7.76 (1H, brs).

Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1,3,4-oxadiazol-2-yl Ketone O-methyloxime

[0607] Ethyl orthoformate (2 ml) was added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetohydrazide (0.49 g, 1.5 mmol), and the mixture was stirred under reflux for 4 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 1,3,4-oxadiazol-2-yl ketone O-methyloxime (0.10 g, 19.8%) as colorless crystals.

[0608] mp. 134-135° C.

[0609]¹H-NMR (CDCl₃) δ ppm: 2.08 (3H, s), 2.25 (3H, s), 4.08 (3H, s), 4.96 (2H, s), 6.54 (1H, s), 6.65 (1H, d, J=7.3), 6.97 (1H, d, J=7.9), 7.32-7.64 (4H, m), 8.93 (1H, s).

Example 10 Synthesis of α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime

[0610] 28% sodium methoxide/methanol solution (1.31 g, 6.8 mmol) was added to a mixture of hydroxylamine hydrochloride (0.47 g, 6.8 mmol) and methanol (10 ml) under ice-cooling over 5 minutes. Then, 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (1.02 g, 3.4 mmol) was added, and the mixture was stirred under reflux for 1.5 hours. After completion of the reaction, water (200 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime (0.87 g, 76.7%) as colorless crystals.

[0611] mp. 200° C. (decomposition)

[0612]¹H-NMR (CDCl₃) δ ppm: 3.92 (3H, s), 4.93 (2H, s), 5.04 (2H, brs), 6.79-6.87 (2H, m), 7.15-7.21 (3H, m), 7.33-7.52 (3H, m).

Synthesis of 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-3-yl Ketone O-methyloxime

[0613] Ethyl orthoformate (2 ml) was added to α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime (0.40 g, 1.2 mmol), and the mixture was stirred under reflux for 4 hours. After completion of the reaction, toluene (10 ml) was added, and the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.36 g, 87.3%) as colorless crystals.

[0614] mp. 107-108° C.

[0615]¹H-NMR (CDCl₃) δ ppm: 4.08 (3H, s), 4.96 (2H, s), 6.72-6.75 (2H, m), 7.14-7.18 (2H, m), 7.28-7.60 (4H, m), 8.76 (1H, s).

Example 11 Synthesis of 2-(4-chlorophenoxymethyl)phenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime

[0616] Acetic anhydride (2 ml) was added α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime (0.40 g, 1.2 mmol), and the mixture was stirred under reflux for 5 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, ether (100 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (50 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.35 g, 81.5%) as colorless crystals.

[0617] mp. 125-126° C.

[0618]¹H-NMR (CDCl₃) δ ppm: 2.65 (3H, s), 4.07 (3H, s), 4.96 (2H, s), 6.74-6.77 (2H, m), 7.15-7.18 (2H, m), 7.26-7.59 (4H, m).

Example 12 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1H-tetrazol-5-yl Ketone O-methyloxime

[0619] Sodium azide (1.30 g, 20=mol), ammonium chloride (1.07 g, 20 mmol) and dimethylformamide (10 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetonitrile (0.59 g, 2 mmol), and the mixture was stirred at 115° C. for 9 hours. After completion of the reaction, ethyl acetate (150 ml) was added, and the mixture was washed with saturated brine (100 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 1H-tetrazol-5-yl ketone O-methyloxime (0.59 g, 87.4%) as colorless crystals.

[0620] mp. 168-170° C.

[0621]¹H-NMR (CDCl₃) δ ppm: 2.00 (3H, s), 2.25 (3H, s), 4.05 (3H, s), 4.95 (2H, s), 6.52 (1H, s), 6.65 (1H, d, J=7.3), 6.96 (1H, d, J=7.3), 7.32-7.63 (4H, m).

Example 13 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methyl-1H-tetrazol-5-yl Ketone O-methyloxime and 2-(2,5-dimethylphenoxymethyl)phenyl 2-methyl-2H-tetrazol-5-yl Ketone O-methyloxime

[0622] Dimethylformamide (3 ml) and potassium carbonate (0.33 g, 2.4 mmol) were added to 2-(2,5-dimethylphenoxymethyl)phenyl 1H-tetrazol-5-yl ketone O-methyloxime (0.40 g, 1.2 mmol), and the mixture was stirred at room temperature for 5 minutes. Then, dimethyl sulfate (0.23 g, 1.8 mmol) was added under ice-cooling, and the mixture was stirred at room temperature overnight. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with brine (50 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 1-methyl-1H-tetrazol-5-yl ketone O-methyloxime as colorless crystals (0.16 g, 37.9%) [mp. 115.5-116.5° C.; ¹H-NMR (CDCl₃) δ ppm: 1.97 (3H, s), 2.26 (3H, s), 4.06 (3H, s), 4.13 (3H, s), 4.89 (2H, s), 6.50 (1H, s), 6.65 (1H, d, J=7.9), 6.97 (1H, d, J=7.9), 7.34-7.58 (4H, m)] and 2-(2,5-dimethylphenoxymethyl)phenyl 2-methyl-2H-tetrazol-5-yl ketone O-methyloxime as colorless crystals (0.08 g, 19.0%) [mp. 131-132° C.; ¹H-NMR (CDCl₃) δ ppm: 2.12 (3H, s), 2.24 (3H, s), 4.09 (3H, s), 4.34 (3H, s), 4.96 (2H, s), 6.54 (1H, s), 6.64 (1H, d, J=7.9), 6.98 (1H, d, J=7.3), 7.29-7.53 (3H, m), 7.69 (1H, d, J=7.3)].

Example 14 Synthesis of 2-(3-chlorophenoxymethyl)phenyl 1-methyl-2-imidazolin-2-yl Ketone O-methyloxime

[0623] Xylene (5 ml) and benzene (5 ml) were added to 2-(3-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (1.0 g, 3.3 mmol), N-methylethylenediamine (740 mg, 10 mmol) and zinc acetate dihydrate (100 mg, 0.46 mmol), and the mixture was subjected to azeotropic dehydration and stirred at 140° C. for 18 hours. After allowing the mixture to stand for cooling, ethyl acetate was added to the reaction mixture. The mixture was washed successively with water and saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on activated alumina containing water (5%) (ethyl acetate/n-hexane) and column chromatography on silica gel (ethyl acetate/n-hexane) to give isomer A (720 mg, 60%, as an oil) and isomer B (220 mg, 19%, as an oil) of 2-(3-chlorophenoxymethyl)phenyl 1-methyl-2-imidazolin-2-yl ketone O-methyloxime.

[0624] Isomer A: ¹H-NMR (CDCl₃) δ ppm: 2.75 (3H, s), 3.41 (2H, t, J=9.8), 3.92 (2H, t, J=9.8), 3.97 (3H, s), 5.35 (2H, s), 6.84 (1H, ddd, J=8.0, 2.4, 0.9), 6.93 (1H, ddd, J=8.0, 1.8, 0.9), 6.99 (1H, dd, J=2.4, 1.8), 7.19 (1H, t, J=8.0), 7.32-7.44 (2H, m), 7.51 (1H, dd, J=7.3, 1.4), 7.64 (1H, d, J=7.0).

[0625] Isomer B: ¹H-NMR (CDCl₃) δ ppm: 3.03 (3H, s), 3.38 (2H, t, J=9.9), 3.77 (2H, t, J=9.9), 3.97 (3H, s), 4.99 (2H, s), 6.83 (1H, dd, J=8.5, 2.5), 6.91 (1H, d, J=7.8), 6.94 (1H, brs), 7.16 (1H, dd, J=8.3, 7.8), 7.23 (1H, d, J=7.6), 7.34-7.39 (2H, m), 7.49 (1H, d, J=6.4).

Example 15 Synthesis of 2-(3-methylphenoxymethyl)phenyl 2-oxazolin-2-yl Ketone O-methyloxime

[0626] Ethylene glycol (2 ml) and benzene (10 ml) were added to 2-(3-methylphenoxymethyl)-α-methoxyiminophenylacetonitrile (1.0 g, 3.6 mmol), 2-aminoethanol (400 mg, 6.6 mmol) and zinc acetate dihydrate (100 mg, 0.46 mmol), and the mixture was subjected to azeotropic dehydration and stirred at 100° C. for 20 hours. After allowing the mixture to stand for cooling, ethyl acetate was added to the reaction mixture. The mixture was washed successively with water and saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2-(3-methylphenoxymethyl)phenyl 2-oxazolin-2-yl ketone O-methyloxime (280 mg, 24%) as an oil.

[0627]¹H-NMR (CDCl₃) δ ppm: 2.31 (3H, s), 4.00 (2H, t, J=9.8), 4.03 (3H, s), 4.32 (2H, t, J=9.8), 5.21 (2H, s), 6.72-6.78 (3H, m), 7.14 (1H, t, J=7.6), 7.31-7.48 (3H, m), 7.62 (1H, d, J=7.6).

Example 16 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 2-thiazolin-2-yl Ketone O-methyloxime

[0628] 2-Aminoethanethiol hydrochloride (2.80 g, 24.6 mmol), zinc acetate dihydrate (600 mg, 2.7 mmol), toluene (12 ml) and triethylamine (3.12 g, 30.8 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetonitrile (6.00 g, 20.4 mmol), and the mixture was stirred under reflux for 14 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl 2-thiazolin-2-yl ketone O-methyloxime (5.71 g, 79.0%) as crystals.

[0629] mp. 79-82° C.

[0630]¹H-NMR (CDCl₃) δ ppm: 2.24 (2.23) (3H, s), 2.29 (2.28) (3H, s), 3.21 (3.27) (2H, t, J=8.6), 4.07 (4.02) (3H, s), 4.24 (3.36) (2H, t, J=8.6), 5.11 (4.93) (2H, s), 6.56-7.63 (7H, m).

Example 17 Synthesis of 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde

[0631] 1M diisobutylaluminum hydride/toluene solution (5.5 ml, 5.5 mmol) was added dropwise to a mixture of methyl 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetate (1.64 g, 5 mmol) and dichloromethane (15 ml) at −70° C. over 0.5 hours, and then the mixture was stirred at −70° C. to room temperature for 3 hours. Methanol (3 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The precipitated insoluble materials were removed, and the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde (0.54 g, 36.3%) as a colorless oil.

[0632]¹H-NMR (CDCl₃) δ ppm: 2.16 (3H, s), 2.28 (3H, s), 4.11 (3H, s), 4.86 (2H, s), 6.55 (1H, s), 6.67 (1H, d, J=7.3), 6.99-7.58 (5H, m), 9.69 (1H, s).

Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl. oxazol-5-yl Ketone O-methyloxime

[0633] p-Toluenesulfonylmethylisocyanide (0.23 g, 1.2 mmol), potassium carbonate (0.18 g, 1.3 mmol) and methanol (2 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde (0.30 g, 1 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl oxazol-5-yl ketone O-methyloxime (0.15 g, 44.6%) as colorless crystals.

[0634] mp. 90-91° C.

[0635]¹H-NMR (CDCl₃) δ ppm: 2.12 (3H, s), 2.24 (3H, s), 4.01 (3H, s), 4.96 (2H, s), 6.54 (1H, s), 6.65 (1H, d, J=7.3), 6.88 (1H, s), 6.98 (1H, d, J=7.3), 7.24-7.69 (4H, m), 7.94 (1H, s).

Example 18 Synthesis of 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl Ketone O-methyloxime

[0636] Zinc acetate dihydrate (400 mg, 1.8 mmol), ethanolamine (975 mg, 15.9 mol) and xylene (8 ml) were added to 2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile (4.00 g, 13.3 mmol), and the mixture was stirred under reflux for 63 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (1.31 g, 28.6%, as crystals) and isomer B (0.45 g, 9.8%, as crystals) of 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime.

[0637] Isomer A: mp. 97-100° C.

[0638]¹H-NMR (CDCl₃) δ ppm: 3.73 (2H, t, J=7.9), 3.96 (2H, t, J=7.9), 4.07 (3H, s), 5.00 (2H, s), 6.92-7.65 (8H, m).

[0639] Isomer B: mp. 109-112° C.

[0640]¹H-NMR (CDCl₃) δ ppm: 3.92 (2H, t, J=9.8), 4.02 (3H, s), 4.39 (2H, t, J=9.8), 5.07 (2H, s), 6.94-7.46 (8H, m).

Synthesis of 2-hydroxyphenyl 2-oxazolin-2-yl Ketone O-methyloxime

[0641] Anisole (152 ml) and aluminium chloride (16.3 g, 122 mmol) were added to 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (19.08 g, 55.3 mmol), and the mixture was stirred under ice-cooling for 1.5 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (6.82 g, 56%) as an oil.

[0642]¹H-NMR (CDCl₃) δ ppm: 4.07 (3H, s), 4.15 (2H, t, J=9.5), 4.50 (2H, t, J=9.5), 6.85-7.35 (5H, m).

Synthesis of 2-(5-trifluoromethyl-2-pyridyloxy)-phenyl 2-oxazolin-2-yl Ketone O-methyloxime

[0643] DMF (2.2 ml), potassium carbonate (210 mg, 1.5 mmol) and 2-chloro-5-trifluoromethylpyridine (220 mg, 1.2 mmol) were added to 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (220 mg, 1.0 mmol), and the mixture was stirred at 100° C. for 2.5 hours. After completion of the reaction, 1N NaOH (100 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(5-trifluoromethyl-2-pyridyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (190 mg, 52.1%) as an oil.

[0644]¹H-NMR (CDCl₃) δ ppm: 3.78 (2H, t, J=9.8), 3.98 (3H, s), 4.16 (2H, t, J=9.8), 6.94-7.87 (6H, m), 8.43 (1H, brs).

[0645] Isomer A: mp. 97-100° C.

[0646]¹H-NMR (CDCl₃) δ ppm: 3.73 (2H, t, J=7.9), 3.96 (2H, t, J=7.9), 4.07 (3H, s), 5.00 (2H, s), 6.92-7.65 (8H, m).

[0647] Isomer B: mp. 109-112° C.

[0648]¹H-NMR (CDCl₃) δ ppm: 3.92 (2H, t, J=9.8), 4.02 (3H, s), 4.39 (2H, t, J=9.8), 5.07 (2H, s), 6.94-7.46 (8H, m).

Synthesis of 2-hydroxyphenyl 2-oxazolin-2-yl Ketone O-methyloxime

[0649] Anisole (152 ml) and aluminium chloride (16.3 g, 122 mmol) were added to 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (19.08 g, 55.3 mmol), and the mixture was stirred under ice-cooling for 1.5 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (6.82 g, 56.0%) as an oil.

[0650]¹H-NMR (CDCl₃) δ ppm: 4.07 (3H, s), 4.15 (2H, t, J=9.5), 4.50 (2H, t, J=9.5), 6.85-7.35 (5H, m).

Synthesis of 2-(5-trifluoromethyl-2-pyridyloxy)-phenyl 2-oxazolin-2-yl Ketone O-methyloxime

[0651] DMF (2.2 ml), potassium carbonate (210 mg, 1.5 mmol) and 2-chloro-5-trifluoromethylpyridine (220 mg, 1.2 mmol) were added to 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (220 mg, 1.0 mmol), and the mixture was stirred at 100° C. for 2.5 hours. After completion of the reaction, 1N NaOH (100 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(5-trifluoromethyl-2-pyridyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (190 mg, 52.1%) as an oil.

[0652]¹H-NMR (CDCl₃) δ ppm: 3.78 (2H, t, J=9.8), 3.98 (3H, s), 4.16 (2H, t, J=9.8), 6.94-7.87 (6H, m), 8.43 (1H, brs).

Example 19 Synthesis of 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile

[0653] Dimethyl sulfoxide (3 ml) and 95% sodium cyanide (0.31 g, 6 mmol) were added to 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminobenzyl chloride (1.03 g, 3 mmol), and the mixture was stirred at 100° C. for 4 hours. After completion of the reaction, ethyl acetate (150 ml) was added, and the mixture was washed with saturated brine (100 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile (0.92 g, 91.5%) as crystals.

[0654]¹H-NMR (CDCl₃) δ ppm: 4.20 (3H, s), 5.15 (2H, s), 6.90-7.41 (6H, m), 7.52 (1H, d, J=2.4).

Synthesis of 5-chloro-2-(4-chlorobenzyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime

[0655] 28% sodium methoxide/methanol solution (1.04 g, 5.4 mmol) was added to a mixture of hydroxylamine hydrochloride (0.38 g, 5.4 mmol) and methanol (6 ml) under ice-cooling over 5 minutes. Then, 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile (0.91 g, 2.7 mmol) was added, and the mixture was stirred under reflux for 1.5 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give α-amino-5-chloro-2-(4-chlorobenzyloxy)-α-hydroxyiminoacetophenone O-methyloxime as a crude product.

[0656] Acetic anhydride (2 ml) was added to the crude product, and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, ethyl acetate (100 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (80 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 5-chloro-2-(4-chlorobenzyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.35 g, 33.0%) as colorless crystals.

[0657] mp. 127-128.5° C.

[0658]¹H-NMR (CDCl₃) δ ppm: 2.38 (3H, s), 4.12 (3H, s), 4.85 (2H, s), 6.84-7.61 (7H, m).

Synthesis of 5-chloro-2-hydroxyphenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime

[0659] Aluminium chloride (0.27 g, 2 mmol) was added to a mixture of 5-chloro-2-(4-chlorobenzyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.39 g, 1 mmol) and anisole (3 ml) under ice-cooling, and the mixture was stirred at the same temperature for 1 hour. After completion of the reaction, aqueous sodium bicarbonate solution (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 5-chloro-2-hydroxyphenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.22 g, 82.2%) as colorless crystals. A part of the crystals was recrystallized from ether/n-hexane to give crystals (mp. 92-93.5° C.)

[0660]¹H-NMR (CDCl₃) δ ppm: 2.75 (3H, s), 4.06 (3H, s), 6.82-7.27 (3H, m), 10.22 (1H, s).

Synthesis of 5-chloro-2-(5-trifluoromethyl-2-pyridyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime

[0661] Dimethylformamide (1 ml), potassium carbonate (0.10 g, 0.74 mmol) and 5-trifluoromethyl-2-chloropyridine (0.10 g, 0.56 mmol) were added to 5-chloro-2-hydroxyphenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.10 g, 0.37 mmol), and the mixture was stirred at 110° C. for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with saturated brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 5-chloro-2-(5-trifluoromethyl-2-pyridyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.14 g, 91.7%) as a colorless oil.

[0662]¹H-NMR (CDCl₃) δ ppm: 2.46 (3H, s), 4.03 (3H, s), 6.77 (1H, d, J=9.2), 7.16 (1H, d, J=9.2), 7.44-7.86 (3H, m), 8.36 (1H, d, J=1.8).

Example 20 Synthesis of 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetonitrile

[0663] Dimethyl sulfoxide (2 ml) and 95% sodium cyanide (0.21 g, 0.004 mol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminobenzyl chloride (0.60 g, 0.002 mol), and the mixture was stirred at 110° C. for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with water twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)-αmethoxyiminophenylacetonitrile (0.45 g, 76.4%) as colorless crystals.

[0664]¹H-NMR (CDCl₃) δ ppm: 2.24 (s, 3H), 2.30 (s, 3H) 4.13 (s, 3H), 5.26 (s, 2H), 6.62-7.76 (m, 7H).

Example 21 Synthesis 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile

[0665] Trifluoroacetic anhydride (3.15 g, 15 mmol) was added to a mixture of 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetamide (1.19 g, 6 mmol) and pyridine (12 ml) under ice-cooling over 20 minutes, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with 1N hydrochloric acid (150 ml), water (100 ml) and saturated aqueous sodium bicarbonate solution (100 ml). The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (1.57 g, 87.0%) as colorless crystals.

[0666] mp. 69-71° C.

[0667]¹H-NMR (CDCl₃) δ ppm: 4.02 (3H, s), 4.99 (2H, s), 6.86-6.89 (2H, m), 7.23-7.26 (2H, m), 7.36-7.56 (4H, m).

Example 22 Synthesis of α-methoxyimino-2-methylphenylacetonitrile

[0668] 85% potassium hydroxide (4.0 g, 61 mmol) and 2-methylphenylacetonitrile (6.6 g, 50 mmol) were added to toluene (33 ml), and the mixture was ice-cooled. Methanol (6.6 ml) was added dropwise, and then butyl nitrite (7.0 ml, 60 mmol) was added dropwise while maintaining the temperature of the mixture at 25 to 35° C. The resulting mixture was stirred under ice-cooling for 3 hours. After allowing the mixture to stand at room temperature overnight, water was added to the reaction mixture, and the resulting potassium salt of α-hydroxyimino-2-methylphenylacetonitrile was extracted. Water was added to the extract to a volume of 100 ml. Toluene (50 ml) and tetrabutylammonium bromide (800 mg, 2.5 mmol) were added, and dimethyl sulfate (5.7 ml, 60 mmol) was added under ice-cooling in 4 divided portions. The mixture was stirred at room temperature for additional 30 minutes, and then the organic layer was separated, washed successively with aqueous 1N sodium hydroxide solution and saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give two geometrical isomers A (6.0 g, 69%, as an oil) and B (1.2 g, 14%, as an oil) of α-methoxyimino-2-methylphenylacetonitrile.

[0669] Isomer A: ¹H-NMR (CDCl₃) δ ppm: 2.51 (3H, s), 4.20 (3H, s), 7.25-7.36 (3H, m), 7.54 (1H, d, J=7.9).

[0670] Isomer B: ¹H-NMR (CDCl₃) δ ppm: 2.31 (3H, s), 4.06 (3H, s), 7.25-7.39 (4H, m).

Synthesis of 2-bromomethyl-α-methoxyiminophenylacetonitrile

[0671] Benzene (80 ml) was added to α-methoxyimino-2-methylphenylacetonitrile (isomer A) (4.0 g, 23 mmol) and N-bromosuccinimide (4.9 g, 28 mmol), and the mixture was heated under reflux for 1 hour in the presence of azobisisobutyronitrile (190 mg, 1.2 mmol) as a radical initiator. After allowing the mixture to stand for cooling, n-hexane (100 ml) was added, and the mixture was allowed to stand overnight, and the resulting insoluble materials were filtered off. The filtrate was concentrated to dryness under reduced pressure and purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2-bromomethyl-α-methoxyiminophenyl-acetonitrile (4.4 g, 76%) as an oil.

[0672]¹H-NMR (CDCl₃) δ ppm: 4.30 (3H, s), 4.79 (2H, s), 7.42-7.50 (3H, m), 7.66-7.69 (1H, m).

Synthesis of 2-(3-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile

[0673] 2-Bromomethyl-α-methoxyiminophenylacetonitrile (5.0 g, 20 mmol) and 3-chlorophenol (3.0 g, 23 mmol) were dissolved in dimethylformamide (25 ml), and the mixture was stirred at room temperature for 2 hours in the presence of potassium carbonate (3.3 g, 24 mmol). After completion of the reaction, diethyl ether (ca. 100 ml) was added to the reaction mixture, and the mixture was washed successively with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) and crystallized from diethyl ether/n-hexane to give 2-(3-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (3.7 g, 62%) as colorless crystals.

[0674] mp. 62-63° C.

[0675]¹H-NMR (CDCl₃) δ ppm: 4.11 (3H, s), 5.25 (2H, s), 6.82 (1H, d, J=8.3), 6.95-6.97 (2H, m), 7.21 (1H, t, J=8.3), 7.45-7.53 (2H, m), 7.67 (1H, d, J=7.3), 7.75 (1H, dd, J=7.3, 1.5).

Example 23 Synthesis of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene

[0676] Pyridinium p-toluenesulfonate (0.30 g, 0.0012 mol) was added to a solution of 2-bromobenzylalcohol (25 g, 0.134 mol) in dichloromethane (100 ml), and the mixture was stirred at room temperature. 3,4-Dihydro-2H-pyran (16.86 g, 0.20 mol) was added thereto. The mixture was stirred at room temperature for 2 hours. Then, saturated aqueous sodium bicarbonate solution (200 ml) was added, and the mixture was extracted with dichloromethane (200 ml). After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the desired 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (36.00 g, yield: 99.3%) as an oil.

[0677]¹H-NMR (CDCl₃) δ ppm: 1.45-1.80 (6H, m), 3.45-3.55 (1H, m), 3.80-3.90 (1H, m), 4.52 (1H, d, J=15.0), 4.80 (1H, m), 4.90 (1H, d, J=15.0), 7.16 (1H, t, J=7.3), 7.31 (1H, t, J=7.3), 7.51 (1H, d, J=7.3), 7.54 (1H, d, J=7.3).

Example 24 Synthesis of 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl Ketone

[0678] Magnesium (0.73 g, 0.03 mol) and bromoethane (0.2 ml) were added to a mixture of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (5.42 g, 0.02 mol) and THF (50 ml) under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 60° C. for 1 hour to prepare Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-3, N-dimethyl-5-isoxazolcarboxamide (3.40 g, 0.02 mol) and THF (40 ml). The mixture was stirred at −60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, yield: 67.9%) as a colorless oil.

[0679]¹H-NMR (CDCl₃) δ ppm: 1.41-1.74 (6H, m), 2.39 (3H, s), 3.45-3.51 (1H, m), 3.75-3.83 (1H, m), 4.59-4.60 (1H, m), 4.71 (1H, d, J=12.8), 4.94 (1H, d, J=12.8), 6.69 (1H, s), 7.38-7.63 (4H, m).

Example 25 Synthesis of 2-hydroxymethylphenyl 3-methylisoxazol-5-yl Ketone O-methyloxime

[0680] Methanol (25 ml), methoxyamine hydrochloride (2.17 g, 0.026 mol) and pyridine (2.1 ml, 0.026 mol) were added to 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, 0.013 mol), and the mixture was stirred under reflux for 3 hours. After completion of the reaction, half-saturated brine (200 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.63 g, yield: 19.7%, as a colorless oil) and isomer B (1.62 g, yield: 50.7%, as a colorless oil) of 2-hydroxymethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime.

[0681] Isomer A: ¹H-NMR (CDCl₃) δ ppm: 2.39 (3H, s), 2.74 (1H, t, J=6.7), 4.17 (3H, s), 4.54 (2H, d, J=6.7), 7.02 (1H, s), 7.33-7.55 (4H, m)

[0682] Isomer B: ¹H-NMR (CDCl₃) δ ppm: 1.89 (1H, t, J=6.1), 2.28 (3H, s), 4.03 (3H, s), 4.52 (2H, d, J=6.1), 6.05 (1H, s), 7.17-7.62 (4H, m).

Example 26 Synthesis of 2-(3-chloro-5-trifluoromethyl-2-pyridyloxymethyl)phenyl 3-methylisoxazol-5-yl Ketone O-methyloxime

[0683] THF (7.5 ml), 2,3-dichloro-5-trifluoromethylpyridine (0.81 g, 3.75 mmol) and 60% sodium hydride (0.12 g, 3.0 mmol) were added to 2-hydroxymethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.62 g, 2.5 mmol) under ice-cooling, and the mixture was stirred at room temperature overnight. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ether (150 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.29 g, yield: 27.2%) and isomer B (0.76 g, yield: 71.4%) of 2-(3-chloro-5-trifluoromethyl-2-pyridyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone O-methyloxime.

[0684] Isomer A: mp. 77-79° C., ¹H-NMR (CDCl₃) δ ppm: 2.37 (3H, s), 4.14 (3H, s), 5.45 (2H, s), 6.97 (1H, s), 7.36-7.63 (4H, m), 7.79 (1H, d, J=2.4), 8.09 (1H, d, J=2.4).

[0685] Isomer B: ¹H-NMR (CDCl₃) δ ppm: 2.28 (3H, s), 4.04 (3H, s), 5.33 (2H, s), 6.01 (1H, s), 7.20-7.65 (4H, m), 7.80 (1H, d, J=2.2), 8.08 (1H, d, J=2.2).

Example 27 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl thiazolidin-2-yl Ketone O-methyloxime

[0686] Toluene (3 ml), butanol (3 ml), cysteamine hydrochloride (0.34 g, 3.0 mmol) and triethylamine (0.42 ml, 3 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetoaldehyde (0.45 g, 1.5 mmol), and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, half-saturated brine (100 ml) was added, and the mixture was extracted with dichloromethane (50 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl thiazolidin-2-yl ketone O-methyloxime (0.49 g, yield 91.6%) as a colorless oil.

[0687]¹H-NMR (CDCl₃) δ ppm: 2.28 (6H, s), 2.40 (1H, brs), 2.81-3.06 (3H, m), 3.38-3.55 (1H, m), 3.87 (3H, s), 4.85-5.50 (3H, m), 6.67-7.64 (7H, m)

Example 28 Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1,3-dioxolan-2-yl Ketone O-methyloxime

[0688] Benzene (4 ml), ethylene glycol (0.12 g, 2.0 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.05 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde (0.3 g, 1.0 mmol), and the mixture was subjected to azeotropic dehydration for 2 hours. After completion of the reaction, half-saturated brine (100 ml) was added, and the mixture was extracted with dichloromethane (50 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl 1,3-dioxolan-2-yl ketone O-methyloxime (0.30 g, yield 87.9%) as colorless crystals. mp 136-137° C.

[0689]¹H-NMR (CDCl₃) δ ppm: 2.28 (3H, m), 2.29 (3H, s), 3.59-3.85 (4H, m), 3.92 (3H, s), 5.04 (1H, s), 5.09 (1H, s), 5.63 (1H, s), 6.66-7.62 (7H, m).

Example 29 Synthesis of 1-bromo-2-(1-ethoxyethyl)oxymethylbenzene

[0690] Pyridinium p-toluenesulfonate (0.50 g, 0.002 mol) was added to a mixture of 2-bromobenzylalcohol (18.70 g, 0.1 mol), dichloromethane (150 ml) and ethyl vinyl ether (14.42 g, 0.2 mol) under ice-cooling, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, half-saturated aqueous sodium bicarbonate solution (300 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 1-bromo-2-(1-ethoxyethyl)oxymethylbenzene (25.44 g, yield: 98.2%) as a colorless oil.

[0691]¹H-NMR (CDCl₃) δ ppm: 1.22 (3H, t, J=7.3), 1.41 (3H, t, J=5.5), 3.49-3.77 (2H, m), 4.59 (1H, d, J=12.8), 4.70 (1H, d, J=12.8), 4.87 (1H, q, J=5.5), 7.11-7.55 (4H, m).

Example 30 Synthesis of 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl Ketone

[0692] A mixture of 1-bromo-2-(1-ethoxyethyl)oxymethylbenzene (12.96 g, 0.05 mol) and THF (45 ml) was added to a mixture of magnesium (1.82 g, 0.075 mol) and bromoethane (0.2 ml) and THF (5 ml) at 45 to 55° C. under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 55° C. for 1 hour to prepare a Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-5, N-dimethyl-3-isoxazolcarboxamide (5.62 g, 0.033 mol) and THF (40 ml) cooled to −50° C. The mixture was stirred at −60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetatein-hexane) to give 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone (8.61 g, yield: 90.2%) as a colorless oil.

[0693]¹H-NMR (CDCl₃) δ ppm: 1.16 (3H, t, J=6.7), 1.27 (3H, d, J=5.5), 2.52 (3H, s), 3.43-3.65 (2H, m), 4.68-4.92 (3H, m), 6.50 (1H, s), 7.36-7.84 (4H, m).

Example 31 Synthesis of 2-(l-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl Ketone O-methyloxime

[0694] 2-(1-Ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone (4.34 g, 0.015 mol) was added to a mixture of methanol (30 ml), methoxyamine hydrochloride (2.51 g, 0.03 mol) and 28% sodium methylate/methanol solution (7.23 g, 0.0375 mol), and the mixture was stirred under reflux for 3 hours. After completion of the reaction, half-saturated brine (200 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (4.32 g, yield: 90.5%) as a colorless oil.

[0695]¹H-NMR (CDCl₃) δ ppm: 1.11-1.26 (6H, m), 2.47 (2.43) (3H, s), 3.39-3.60 (2H, m), 4.08 (3.97) (3H, s), 4.11-4.70 (3H, m), 6.61 (6.37) (1H, s), 7.19-7.56 (4H, m).

Example 32 Synthesis of 2-hydroxymethylphenyl 5-methylisoxazol-3-yl Ketone O-methyloxime

[0696] Methanol (26 ml) and pyridinium p-toluenesulfonate (0.33 g, 0.0013 mol) were added to 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (4.14 g, 0.013 mol), and the mixture was stirred under reflux for 0.5 hour. After completion of the reaction, half-saturated brine (300 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-hydroxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (2.95 g, yield: 92.1%) as a colorless oil.

[0697]¹H-NMR (CDCl₃) δ ppm: 2.43 (3.18) (1H, t, J=6.7), 2.44 (2.50) (3H, s), 3.99 (4.11) (3H, s), 4.47 (4.57) (2H, d, J=6.7), 6.44 (6.62) (1H, s), 7.19-7.60 (4H, m).

Example 33 Synthesis of 2-(5-chloro-3-trifluoromethyl-2-pyridyloxymethyl)phenyl 5-methylisoxazol-3-yl Ketone O-methyloxime

[0698] THF (3 ml), 2,5-dichloro-3-trifluoromethylpyridine (0.32 g, 1.5 mmol) and 60% sodium hydride (0.05 g, 1.2 mmol) were added to 2-hydroxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (0.25 g, 1.0 mmol) under ice-cooling, and the mixture was stirred at room temperature overnight. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ether (150 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(5-chloro-3-trifluoromethyl-2-pyridyloxymethyl)phenyl 5-methylisoxazol-3-yl ketone O-methyloxime (0.41 g, yield: 96.3%) as colorless crystals.

[0699] mp. 120-121° C. (ether/n-hexane)

[0700]¹H-NMR (CDCl₃) δ ppm: 2.45 (3H, s), 3.99 (3H, s) , 5.34 (2H, s), 6.39 (1H, s), 7.23-7.64 (2H, m), 7.79 (1H, d, J=2.5), 8.06 (1H, d, J=2.5).

Example 34 Synthesis of 2-chloromethylphenyl 3-methylisoxazol-5-yl Ketone O-methyloxime

[0701] Benzene (5 ml) and thionyl chloride (0.36 g, 3.0 mmol) were added to 2-hydroxymethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.62 g, 2.5 mmol), and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-chloromethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.26 g, yield: 39.3%) as a colorless oil.

[0702]¹H-NMR (CDCl₃) δ ppm: 2.29 (3H, s), 4.04 (3H, s), 4.47 (2H, s), 6.05 (1H, s), 7.18-7.60 (4H, m).

Example 35 Synthesis of 2-(3,4-dichloro-α-methylbenzylideneaminooxymethyl)phenyl 3-methylisoxazol-5-yl Ketone O-methyloxime

[0703] DMF (3 ml), 3,4-dichloroacetophenone oxime (0.31 g, 1.5 mmol) and potassium carbonate (0.28 g, 2.0 mmol) were added to 2-chloromethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.26 g, 1.0 mmol), and the mixture was stirred at 60° C. for 2 hours. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ether (150 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(3,4-dichloro-α-methylbenzylideneaminooxymethyl)phenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.37 g, yield: 85.6%) as colorless crystals.

[0704]¹H-NMR (CDCl₃) δ ppm: 2.01 (3H, s), 2.21 (3H, s), 4.04 (3H, s), 5.13 (2H, s), 5.96 (1H, s), 7.20-7.64 (7H, m). mp. 84-85° C.

Example 36 Synthesis of 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetaldehyde

[0705] 1M diisobutylaluminum hydride/toluene solution (11 ml, 16.5 mmol) was added dropwise to a mixture of methyl 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetate (4.83 g, 11.8 mmol) and dichloromethane (47 ml) at −65° C. or lower over 4 minutes, and the mixture was stirred at −78° C. to room temperature for 3 hours. Methanol (7 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The precipitated insoluble materials were removed, and the remaining mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetaldehyde (2.11 g, 47.3%) as a colorless oil.

[0706]¹H-NMR (CDCl₃) δ ppm: 2.19 (3H, s), 4.11 (3H, s), 5.09 (2H, s), 7.09-7.12 (1H, m), 7.36-7.52 (4H, m), 7.59 (1H, d, J=7.9), 7.77 (1H, d, J=7.9), 7.85 (1H, s), 9.70 (1H, s).

Example 37 Synthesis of 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]phenyl Thiazolidin-2-yl Ketone O-methyloxime

[0707] Toluene (2.5 ml), butanol (2.5 ml), cysteamine hydrochloride (0.29 g, 2.54 mmol) and triethylamine (0.26 g, 2.54 mmol) were added to 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetaldehyde (0.48 g, 1.27 mmol), and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, half-saturated brine (100 ml) was added, and the mixture was extracted with dichloromethane (50 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]phenyl thiazolidin-2-yl ketone O-methyloxime (0.52 g, yield 93.6%) as a colorless oil.

[0708]¹H-NMR (CDCl₃) δ ppm: 2.39 (3H, s), 2.75-3.10 (3H, m), 3.50 (2H, m), 3.86 (3H, s), 5.20-5.30 (2H, m), 5.45 (1H, m), 7.37-7.61 (6H, m), 7.82 (1H, d, J=7.9), 7.91 (1H, s).

[0709] According to the same manner as that in Examples 24 and 30, various compounds of the formula (XLVIII), which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds (XLVIII-7) and (XLVIII-4) obtained in Examples 24 and 30, respectively, are also listed. No R³ R⁴ P Physical data XLVIII-1 Isoxazol-3-yl H Tetrahydropyranyl XLVIII-2 Isoxazol-3-yl H 1-C₂H₅OC₂H₄ ¹H-NMR(CDCl₃)δppm :1.16(3H, t, J=7.3), 1.26(3H, d, J=5.5), 3.40- 3.65(2H, m), 4.70-4.93(3H, m), 6.89(1H, d, J=1.8), 7.37-7.87(4H, m), 8.53(1H, J=1.8) XLVIII-3 5-Me- H Tetrahydropyranyl Isoxazol-3-yl XLVIII-4 5-Me- H 1-C₂H₅OC₂H₄ ¹H-NMR(CDCl₃)δppm: 1.16(3H, t, isoxazol-3-yl J=6.7), 1.27(3H, d, J=5.5), 2.52(3H, s), 3.43-3.65(2H, m), 4.68-4.92(3H, m), 6.50(1H, s), 7.36-7.84(4H, m). XLVIII-5 Isoxazol-5-yl H Tetrahydropyranyl XLVIII-6 Isoxazol-5-yl H 1-C₂H₅OC₂H₄ XLVIII-7 3-Me- H Tetrahydropyranyl ¹H-NMR(CDCl₃)δppm: 1.41-1.74 soxazol-5-yl (6H, m), 2.39(3H, s), 3.45-3.51(1H, m), 3.75-3.83(1 H, m), 4.59-4.60 (1H, m), 4.71(1H, d, J=12.8), 4.94 (1H, d, J=12.8), 6.69(1H, s), 7.38- 7.63(4H, m). XLVIII-8 3-Me- H 1-C₂H₅OC₂H₄ ¹H-NMR(CDCl₃)δppm: 1.16(3H, t, isoxazol-5-yl J=7.3), 1.25(3H, d, J=5.5), 2.40(3H, s), 3.42-3.61(2H, m), 4.68-4.88(3H, m), 6.70(1H, s), 7.37-7.66(4H, m) XLVIII-9 1,3,4- H Tetrahydropyranyl Oxadiazol-2-yl XLVIII-10 1,3,4- Oxadiazol-2-yl H 1-C₂H₅OC₂H₄ XLVIII-11 1-Me-imidazol- H Tetrahydropyranyl 2-yl XLVIII-12 1-Me-imidazol- H 1-C₂H₅OC₂H₄ 2-yl XLVIII-13 2-Isoxazolin-3- H Tetrahydropyranyl yl XLVIII-14 2-Isoxazolin-3- H 1-C₂H₅OC₂H₄ yl XLVIII-15 5-Me-2- H Tetrahydropyranyl isoxazolin-3-yl XLVIII-16 5-Me-2- H 1-C₂H₅OC₂H₄ isoxazolin-3-yl XLVIII-17 2-Furyl H Tetrahydropyranyl XLVIII-18 2-Furyl H 1-C₂H₅OC₂H₄ XLVIII-19 5-Me-1,2,4- H Tetrahydropyranyl oxadiazol-3-yl XLVIII-20 5-Me-1,2,4- H 1-C₂H₅OC₂H₄ oxadiazol-3-yl

[0710] According to the same manner as that in Examples described above, various compounds of the formula (I) were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds obtained in the above Examples are also listed. “No.” represents a compound number. When the product is obtained as a mixture of isomers A/B, the δ values of either isomer are indicated in the parentheses.

[0711] The basic structures of the compound (I) in the tables are as follows:

No R¹ R² R³ n Physical data 1 C₆H₅ Me Imidazol-1-yl 1 mp 66-67.5° C. 2 2-F—C₆H₄ Me Imidazol-1-yl 1 3 3-F—C₆H₄ Me Imidazol-1-yl 1 4 4-F—C₆H₄ Me Imidazol-1-yl 1 5 2-Cl—C₆H₄ Me Imidazol-1-yl 1 mp 79.5--80.5° C. 6 3-Cl—C₆H₄ Me Imidazol-1-yl 1 mp 96.5-97.5° C. 7 4-Cl—C₆H₄ Me Imidazol-1-yl 1 mp 88-88.5° C. 8 2-Br—C₆H₄ Me Imidazol-1-yl 1 9 3-Br—C₆H₄ Me Imidazol-1-yl 1 10 4-Br—C₆H₄ Me Imidazol-1-yl 1 11 3-I—C₆H₄ Me Imidazol-1-yl 1 12 4-I—C₆H₄ Me Imidazol-1-yl 1 13 2-Me—C₆H₄ Me Imidazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.16(3H, s), 3.99(3H, s), 4.98(2H, s), 6.68-7.66(10H, m), 7.96(1H, s) 14 3-Me—C₆H₄ Me Imidazol-1-yl 1 15 4-Me—C₆H₄ Me Imidazol-1-yl 1 mp 58-65° C. 16 2-Et—C₆H₄ Me Imidazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 1.16(3H, t, J=7.3), 2.60(2H, q, J=7.3), 3.99(3H, s), 4.98(2H, s), 6.69-7.67(10H, m), 7.96(1H, s) 17 3-Et—C₆H₄ Me Imidazol-1-yl 1 18 4-Et—C₆H₄ Me Imidazol-1-yl 1 19 2-MeO—C₆H₄ Me Imidazol-1-yl 1 20 3-MeO—C₆H₄ Me Imidazol-1-yl 1 21 4-MeO—C₆H₄ Me Imidazol-1-yl 1 22 2-CF₃—C₆H₄ Me Imidazol-1-yl 1 23 3-CF₃—C₆H₄ Me Imidazol-1-yl 1 24 4-CF₃—C₆H₄ Me Imidazol-1-yl 1 25 2,3-F₂—C₆H₃ Me Imidazol-1-yl 1 26 2,4-F₂—C₆H₃ Me Imidazol-1-yl 1 27 2,5-F₂—C₆H₃ Me Imidazol-1-yl 1 28 2,6-F₂—C₆H₃ Me Imidazol-1-yl 1 29 3,4-F₂—C₆H₃ Me Imidazol-1-yl 1 30 3,5-F₂—C₆H₃ Me Imidazol-1-yl 1 31 2,3-Cl₂—C₆H₃ Me Imidazol-1-yl 1 32 2,4-Cl₂—C₆H₃ Me Imidazol-1-yl 1 33 2,5-Cl₂—C₆H₃ Me Imidazol-1-yl 1 34 2,6-Cl₂—C₆H₃ Me Imidazol-1-yl 1 35 3,4-Cl₂—C₆H₃ Me Imidazol-1-yl 1 36 3,5-Cl₂—C₆H₃ Me Imidazol-1-yl 1 37 2,3-Me₂C₆H₃ Me Imidazol-1-yl 1 38 2,4-Me₂—C₆H₃ Me Imidazol-1-yl 1 39 2,5-Me₂—C₆H₃ Me Imidazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.11(3H, s), 2.26(3H, s), 3.99(3H, s), 4.96(2H, s), 6.52(1H, s), 6.66(1H, d, J=7.3), 6.98-7.66(7H, m), 7.96(1H, s) 40 2,6-Me₂—C₆H₃ Me Imidazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.17(6H, s), 4.01 (3H, s), 4.78(2H, s), 6.89—7.85(9H, m), 8.04(1H, s) 41 3,4-Me₂—C₆H₃ Me Imidazol-1-yl 1 42 3,5-Me₂—C₆H₃ Me Imidazol-1-yl 1 43 2-Cl-4-Me—C₆H₃ Me Imidazol-1-yl 1 44 2-Cl-5-Me—C₆H₃ Me Imidazol-1-yl 1 45 4-Cl-2-Me—C₆H₃ Me Imidazol-1-yl 1 46 4-Cl-3-Me—C₆H₃ Me Imidazol-1-yl 1 47 2,3,5-Me₃—C₆H₂ Me Imidazol-1-yl 1 48 3-Ph—C₆H₄ Me Imidazol-1-yl 1 49 4-Ph—C₆H₄ Me Imidazol-1-yl 1 50 2-i-Pr—C₆H₄ Me Imidazol-1-yl 1 51 3-i-Pr—C₆H₄ Me Imidazol-1-yl 1 52 4-i-Pr—C₆H₄ Me Imidazol-1-yl 1 53 3-t-Bu—C₆H₄ Me Imidazol-1-yl 1 54 4-t-Bu—C₆H₄ Me Imidazol-1-yl 1 55 3-i-PrO—C₆H₄ Me Imidazol-1-yl 1 56 4-i-PrO—C₆H₄ Me Imidazol-1-yl 1 57 2-Cl- Me Imidazol-1-yl 1 mp 107.5-108.5° C. pyridin-3-yl 58 4-MeS—C₆H₄ Me Imidazol-1-yl 1 59 Pyridin-3-yl Me Imidazol-1-yl 1 60 2,4,5-Cl₃—C₆H₂ Me Imidazol-1-yl 1 61 C₆H₅ Et Imidazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 1.30(3H, t, J=6.7), 4.21(2H, q, J=6.7), 5.02(2H, s), 6.78- 7.64(11H, m), 8.04(1H, s) 62 2-F—C₆H₄ Et Imidazol-1-yl 1 63 3-F—C₆H₄ Et Imidazol-1-yl 1 64 4-F—C₆H₄ Et Imidazol-1-yl 1 65 2-Cl—C₆H₄ Et Imidazol-1-yl 1 66 3-Cl—C₆H₄ Et Imidazol-1-yl 1 67 4-Cl—C₆H₄ Et Imidazol-1-yl 1 68 2-Br—C₆H₄ Et Imidazol-1-yl 1 69 3-Br—C₆H₄ Et Imidazol-1-yl 1 70 4-Br—C₆H₄ Et Imidazol-1-yl 1 71 3-I—C₆H₄ Et Imidazol-1-yl 1 72 2-Me—C₆H₄ Et Imidazol-1-yl 1 73 3-Me—C₆H₄ Et Imidazol-1-yl 1 74 4-Me—C₆H₄ Et Imidazol-1-yl 1 75 2-Et—C₆H₄ Et Imidazol-1-yl 1 76 3-Et—C₆H₄ Et Imidazol-1-yl 1 77 4-Et—C₆H₄ Et Imidazol-1-yl 1 78 2-MeO—C₆H₄ Et Imidazol-1-yl 1 79 3-MeO—C₆H₄ Et Imidazol-1-yl 1 80 4-MeO—C₆H₄ Et Imidazol-1-yl 1 81 C₆H₅ Allyl Imidazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.63- 4.66(2H, m), 5.02(2H, s), 5.20- 5.33(2H, m), 5.86-6.01 (1H, m), 6.77-7.64(11H, m), 8.03(1H, s) 82 2-F—C₆H₄ Allyl Imidazol-1-yl 1 83 3-F—C₆H₄ Allyl Imidazol-1-yl 1 84 4-F—C₆H₄ Allyl Imidazol-1-yl 1 85 2-Cl—C₆H₄ Allyl Imidazol-1-yl 1 86 3-Cl—C₆H₄ Allyl Imidazol-1-yl 1 87 4-Cl—C₆H₄ Allyl Imidazol-1-yl 1 88 2-Br—C₆H₄ Allyl Imidazol-1-yl 1 89 3-Br—C₆H₄ Allyl Imidazol-1-yl 1 90 4-Br—C₆H₄ Allyl Imidazol-1-yl 1 91 3-I—C₆H₄ Allyl Imidazol-1-yl 1 92 2-Me—C₆H₄ Allyl Imidazol-1-yl 1 93 3-Me—C₆H₄ Allyl Imidazol-1-yl 1 94 4-Me—C₆H₄ Allyl Imidazol-1-yl 1 95 2-Et—C₆H₄ Allyl Imidazol-1-yl 1 96 3-Et—C₆H₄ Allyl Imidazol-1-yl 1 97 4-Et—C₆H₄ Allyl Imidazol-1-yl 1 98 2-MeO—C₆H₄ Allyl Imidazol-1-yl 1 99 3-MeO—C₆H₄ Allyl Imidazol-1-yl 1 100 4-MeO—C₆H₄ Allyl Imidazol-1-yl 1 101 C₆H₅ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.85(3H, s), 3.95(3H, s), 4.93(2H, s), 6.80-7.57(11H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 3.51(3H, s), 3.99(3H, s), 4.91(2H, s), 6.83-7.57(11H, m) 102 2-F—C₆H₄ Me 1-Me- 1 imidazol-2-yl 103 3-F—C₆H₄ Me 1-Me- 1 imidazol-2-yl 104 4-F—C₆H₄ Me 1-Me- 1 Isomer A: mp 99.5-100.5° C. imidazol-2-yl Isomer B: mp 114.5-115.5  C. 105 2-Cl—C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.91 (3H, s), 3.96(3H, s), 5.04(2H, s), 6.81-7.65(10H, m) Isomer B: mp 146.5-147.5° C. 106 3-Cl—C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.88(3H, s), 3.96(3H, s), 4.94(2H, s), 6.69-7.54(10H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 3.53(3H, s), 4.00(3H, s), 4.94(2H. s), 6.74-7.55(10H, m) 107 4-Cl—C₆H₄ Me 1-Me- 1 Isomer A: mp 122.0-123.0° C. imidazol-2-yl Isomer B: mp 144.5-145.5° C. 108 2-Br—C₆H₄ Me 1-Me- 1 imidazol-2-yl 109 3-Br—C₆H₄ Me 1-Me- 1 imadazol-2-yl 110 4-Br—C₆H₄ Me 1-Me- 1 imidazol-2-yl 111 3-I—C₆H₄ Me 1-Me- 1 imidazol-2-yl 112 2-Me—C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCL₃) δ imidazol-2-yl ppm: 2.18(3H, s), 3.85(3H, s), 3.96(3H, s), 4.93(2H, s), 6.73- 7.60(10H, m) Isomer B: mp 126.0-127.0° C. 113 3-Me—C₆H₄ Me 1-Me- 1 Isomer A: mp 88.0-91.0° C. imidazol-2-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.31 (3H, s), 3.51(3H, s), 4.01(3H, s), 4.89(2H, s), 6.63- 7.65(10H, m) 114 4-Me—C₆H₄ Me 1-Me- 1 Isomer A: mp 105.5-106.5° C. imidazol-2-yl Isomer B: mp 118.5-119.5° C. 115 2-Et—C₆H₄ Me 1-Me- 1 imidazol-2-yl 116 3-Et—C₆H₄ Me 1-Me- 1 imidazol-2-yl 117 4-Et—C₆H₄ Me 1-Me- 1 imidazol-2-yl 118 2-MeO—C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.85(3H, s), 3.91(3H, s), 3.96(3H, s), 5.04(2H, s), 6.74-7.65(10H, m) Isomer B: mp 108.5-109.5° C. 119 3-MeO—C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.74(3H, s), 3.85(3H, s), 3.95(3H, s), 4.91(2H, s), 6.38-7.56(10H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 3.52(3H, s), 3.77(3H, s), 4.00(3H, s), 4.89(2H, s), 6.44- 7.56(10H, m) 120 4-MeO—C₆H₄ Me 1-Me- 1 imidazol-2-yl 121 2-CF₃—C₆H₄ Me 1-Me- 1 imidazol-2-yl 122 3-CF₃—C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.86(3H, s), 3.95(3H, s), 4.99(2H, s), 6.92-7.54(10H, m) Isomer B: mp 106.0-107.0° C. 123 4-CF₃—C₆H₄ Me 1-Me- 1 imidazol-2-yl 124 2,4-F₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 125 2,5-F₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 126 2,6-F₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 127 3,4-F₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 128 3,5-F₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 129 2,3-Cl₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 130 2,4-Cl₂—C₆H₃ Me 1-Me- 1 Isomer A: mp 115.0-116.0° C. imidazol-2-yl Isomer B: mp 157.5-158.5° C. 131 2,5-Cl₂—C₆H₃ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.94(3H, s), 3.98(3H, s), 5.04(2H, s), 6.82-7.65(9H, m) Isomer B: mp 128.5-130.0° C. 132 3,4-Cl₂—C₆H₃ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.91(3H, s), 3.96(3H, s), 4.94(2H, s), 6.67-7.65(9H, m) Isomer B: mp 124.5-125.5° C. 133 3,4-Cl₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 134 2,3-Me₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 135 2,4-Me₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 136 2,5-Me₂—C₆H₃ Me 1-Me- 1 Isomer A¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 2.13(3H, s), 2.24(3H, s), 3.86(3H, s), 3.97(3H, s), 4.92(2H, s), 6.55(1H, s), 6.63(1H, d, J=7.9), 6.91(1H, s), 6.98(1H, d, J=7.9), 7.26(1H, s), 7.29-7.60(4H, m) Isomer B¹H-NMR(CDCl₃) δ ppm: 2.21(3H, s), 2.29(3H, s), 3.49(3H, s), 4.03(3H, s), 4.92(2H, s), 6.53(1 H, s), 6.67(1H, d, J=7.3), 6.95(1H, d, J=1.2), 7.01(1H, d, 7.3), 7.17(1H, d, J=1.2), 7.30- 7.65(4H, m) 137 3,4-Me₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 138 3,5-Me₂—C₆H₃ Me 1-Me- 1 imidazol-2-yl 139 2-Cl-4-Me—C₆H₃ Me 1-Me- 1 imidazol-2-yl 140 2-Cl-5-Me—C₆H₃ Me 1-Me- 1 imidazol-2-yl 1 141 4-Cl-2-Me—C₆H₃ Me 1-Me- 1 Isomer A: mp 87.0-88.0° C. imidazol-2-yl Isomer B: mp 134.0-135.0° C. 142 4-Cl-3-Me—C₆H₃ Me 1-Me- 1 imidazol-2-yl 143 3-Ph—C₆H₄ Me 1-Me- 1 imidazol-2-yl 144 4-Ph—C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 3.87(3H, s), 3.97(3H, s), 4.98(2H, s), 6.88-7.64(15H, m) Isomer B: mpl4l.5-142.5t 145 3-i-PrO—C₆H₄ Me 1-Me- 1 imidazol-2-yl 146 3-i-Pr-C₆H₄ Me 1-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ imidazol-2-yl ppm: 1.20(6H, d, J=7.3), 2.83(1H, sept, J=7.3), 3.82(3H, s), 3.96(3H, s), 4.91(2H, s), 6.61-7.57(10H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 1.23(6H, d, J=7.3), 2.86(1H, sept, J=7.3), 3.50(3H, s), 4.00(3H, s), 4.88(2H, s), 6.64-7.58(10H, m) 147 4-i-Pr—C₆H₄ Me 1-Me- 1 imidazol-2-yl 148 3-t-Bu—C₆H₄ Me 1-Me- 1 imidazol-2-yl 149 2-MeS—C₆H₄ Me 1-Me- 1 imidazol-2-yl 1 150 4-MeS—C₆H₄ Me 1-Me- 1 imidazol-2-yl 151 2,3,6-F₃C₆H₂ Me 1-Me- 1 imidazol-2-yl 152 2,4,5-CL₃—C₆H₂ Me 1-Me- 1 imidazol-2-yl 153 3-PhO—C₆H₄ Me 1-Me- 1 imidazol-2-yl 154 3,4,5-(MeO)₃—C₆H₂ Me 1-Me- 1 imidazol-2-yl 155 2,3,5-Me₃—C₆H₂ Me 1-Me- 1 imidazol-2-yl 156 3,4,5-Me₃—C₆H₂ Me 1-Me- 1 imidazol-2-yl 157 C₆F₅ Me 1-Me- 1 imidazol-2-yl 158 4-Cl-3-Et—C₆H₃ Me 1-Me- 1 imidazol-2-yl 159 3-EtO—C₆H₄ Me 1-Me- 1 imidazol-2-yl 160 4-EtO—C₆H₄ Me 1-Me- 1 imidazol-2-yl 161 C₆H₅ Me 1-Me- 0 ¹H-NMR(CDCl₃) δ ppm: imiazol-2-yl 3.48(3H, s), 4.02(3H, s), 6.67- 7.36(10H, m), 7.75(1H, dd, J=7.3, 1.8) 162 4-F—C₆H₄ Me 1-Me- 0 imidazol-2-yl 163 3-Cl—C₆H₄ Me 1-Me- 0 imidazol-2-yl 164 4-Cl—C₆H₄ Me 1-Me- 0 imidazol-2-yl 165 3-Me—C₆H₄ Me 1-Me- 0 imidazol-2-yl 166 4-Me—C₆H₄ Me 1-Me- 0 imidazol-2-yl 167 4-Et—C₆H₄ Me 1-Me- 0 imidazol-2-yl 168 4-NO₂—C₆H₄ Me 1-Me- 0 imidazol-2-yl 169 3,4-Cl₂—C₆H₃ Me 1-Me- 0 imidazol-2-yl 170 3,5-Cl₂—C₆H₃ Me 1-Me- 0 imidazol-2-yl 171 3,4-Me₂—C₆H₃ Me 1-Me- 0 imidazol-2-yl 172 3,5-Me₂—C₆H₃ Me 1-Me- 0 imidazol-2-yl 173 3-PhO—C₆H₄ Me 1-Me- 0 imidazol-2-yl 174 4-Cl-3-Et—C₆H₃ Me 1-Me- 0 imidazol-2-yl 175 3-EtO—C₆H₄ Me 1-Me- 0 imidazol-2-yl 176 3-CF₃C₆H₄ Me 1-Me- 0 imidazol-2-yl 177 4-CF₃—C₆H₄ Me 1-Me- 0 imidazol-2-yl 178 3-i-PrO—C₆H₄ Me 1-Me- 0 imidazol-2-yl 179 3-i-Pr—C₆H₄ Me 1-Me- 0 imidazol-2-yl 180 4-Cl-3-Me—C₆H₃ Me 1-Me- 0 imidazol-2-yl 181 Pyridin-2-yl Me 1-Me- 1 imidazol-2-yl 182 Pyridin-3-yl Me 1-Me- 1 imidazol-2-yl 183 5-Cl- Me 1-Me- 1 pyridin-2-yl imidazol-2-yl 184 3-Cl- Me 1-Me- 1 pyridin-2-yl imidazol-2-yl 185 6-Cl- Me 1-Me- 1 pyridin-2-yl imidazol-2-yl 186 2-Cl- Me 1-Me- 1 pyridin-3-yl imidazol-2-yl 187 5-CF₃- Me 1-Me- 1 pyridin-2-yl imidazol-2-yl 188 3-CF₃- Me 1-Me- 1 pyridin-2-yl imidazol-2-yl 189 6-CF₃-3-Cl- Me 1-Me- 1 pyridin-2-yl imidazol-2-yl 190 5-CF₃-3-Cl- Me 1-Me- 1 pyridin-2-yl imidazol-2-yl 191 Benzothiazol- Me 1-Me- 1 2-yl imidazol-2-yl 192 Benzoxazol- Me 1-Me- 1 2-yl imidazol-2-yl 193 Quinolin-2-yl Me 1-Me- 1 imidazol-2-yl 194 5-CF₃-1,3,4- Me 1-Me- 1 thiadiazol-2-yl imidazol-2-yl 195 Pyrimidin-2-yl Me 1-Me- 1 imidazol-2-yl 196 5-Cl-6-Me- Me 1-Me- 1 pyrimidin-4-yl imidazol-2-yl 197 5-Et-6-Me- Me 1-Me- 1 pyrimidin-4-yl imidazol-2-yl 198 6-Cl- Me 1-Me- 1 pyrazin-2-yl imidazol-2-yl 199 3,6-Me₂- Me 1-Me- 1 pyrazin-2-yl imidazol-2-yl 200 5-Me- Me 1-Me- 1 isoxazol-3-yl imidazol-2-yl 201 C₆H₅ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 1.95(3H, s), 3.92(3H, s), 5.18(2H, s), 6.86-7.71(11H, m) 202 2-F—C₆H₄ Me 5-Me- 1 imidazol-1-yl 203 3-F—C₆H₄ Me 5-Me- 1 imidazol-1-yl 204 4-F—C₆H₄ Me 5-Me- 1 imidazol-1-yl 205 2-Cl—C₆H₄ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 1.94(3H, d, J=1.2), 3.96(3H, s), 5.24(2H, s), 6.86-7.82(10H, m) 206 3-Cl—C₆H₄ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 1.96(3H, s), 3.93(3H, s), 5.18(2H, s), 6.79-7.67(10H, m) 207 4-Cl—C₆H₄ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 1.94(3H, s), 3.92(3H, s), 5.13(2H, s), 6.82-7.66(10H, m) 208 2-Me—C₆H₄ Me 5-Me- 1 imidazol-1-yl 209 3-Me—C₆H₄ Me 5-Me- 1 imidazol-1-yl 210 4-Me—C₆H₄ Me 5-Me- 1 imidazol-1-yl 211 2-MeO—C₆H₄ Me 5-Me- 1 imidazol-1-yl 212 3-MeO—C₆H₄ Me 5-Me- 1 imidazol-1-yl 213 4-MeO—C₆H₄ Me 5-Me- 1 imidazol-1-yl 214 2,5-Me₂—C₆H₃ Me 5-Me- 1 imidazol-1-yl 215 C₆H₅ Et 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 1.28(3H, t, J=7.3), 1.96(3H, s), 4.19(2H, q, J=7.3), 5.20(2H, s), 6.86-7.72(11H, m) 216 4-Cl—C₆H₄ Et 5-Me- 1 imidazol-1-yl 217 4-Me—C₆H₄ Et 5-Me- 1 imidazol-1-yl 218 C₆H₅ Allyl 5-Me- 1 imidazol-1-yl 219 4-Cl—C₆H₄ Allyl 5-Me- 1 imidazol-1-yl 220 4-Me—C₆H₄ Allyl 5-Me- 1 imidazol-1-yl 221 C₆H₅ Me 4-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 2.19(3H, s), 3.95(3H, s), 5.00(2H, s), 6.79-7.63(10H, m), 7.90(1H ,s) 222 2-F—C₆H₄ Me 4-Me- 1 imidazol-1-yl 223 3-F—C₆H₄ Me 4-Me- 1 imidazol-1-yl 224 4-F—C₆H₄ Me 4-Me- 1 imidazol-1-yl 225 2-Cl—C₆H₄ Me 4-Me- 1 ¹H-NMR(CDCl₃) δ]ppm: imidazol-1-yl 2.18(3H, d, J=1.2), 3.99(3H, s), 5.05(2H, s), 6.77-7.72(9H, m), 7.90(1H, d, J=1.2) 226 3-Cl—C₆H₄ Me 4-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 2.19(3H, s), 3.96(3H, s), 4.99(2H, s), 6.95-7.59(9H, m), 7.88(1H, d, J=1.2) 227 4-Cl—C₆H₄ Me 4-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 2.18(3H, s), 3.95(3H, s), 4.97(2H, s), 6.70-7.59(9H, m), 7.88(1H, d, J=1.2) 228 2-Me—C₆H₄ Me 4-Me- 1 imidazol-1-yl 229 3-Me—C₆H₄ Me 4-Me- 1 imidazol-1-yl 230 4-Me—C₆H₄ Me 4-Me- 1 imidazol-1-yl 231 2-MeO—C₆H₄ Me 4-Me- 1 imidazol-1 yl 232 3-MeO—C₆H₄ Me 4-Me- 1 imidazol-1-yl 4-Me- 233 4-MeO—C₆H₄ Me 4-Me- 1 imidazol-1-yl 234 2,5-Me₂—C₆H₃ Me 4-Me- 1 imidazol-1-yl 235 C₆H₅ Et 4-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 1.30(3H, t, J=7.3), 2.19(3H, s), 4.21(2H, q, J=7.3), 5.02(2H, s), 6.78-7.63(10H, m), 7.96(1H, s) 236 4-Cl—C₆H₄ Et 4-Me- 1 imidazol-1-yl 237 4-Me—C₆H₄ Et 4-Me- 1 imidazol-1-yl 238 C₆H₅ Allyl 4-Me- 1 imidazol-1-yl 239 4-Cl—C₆H₄ Allyl 4-Me- 1 imidazol-1-yl 240 4-Me—C₆H₄ Allyl 4-Me- 1 imidazol-1-yl 241 C₆H₅ Me 2-Me- 1 ¹H-NMR(CDCl₃) δ ppm: imidazol-1-yl 2.21(3H, s), 3.93(3H, s), 5.18(2H, s), 6.89-7.71(11H, m) 242 2-F—C₆H₄ Me 2-Me- 1 imidazol-1-yl 243 3-F—C₆H₄ Me 2-Me- 1 imidazol-1-yl 244 4-F—C₆H₄ Me 2-Me- 1 imidazol-1-yl 245 2-Cl—C₆H₄ Me 2-Me- 1 imidazol-1-yl 246 3-Cl—C₆H₄ Me 2-Me- 1 imidazol-1-yl 247 4-Cl—C₆H₄ Me 2-Me- 1 imidazol-1-yl 248 2-Me—C₆H₄ Me 2-Me- 1 imidazol-1-yl 249 3-Me—C₆H₄ Me 2-Me- 1 imidazol-1-yl 250 4-Me—C₆H₄ Me 2-Me- 1 imidazol-1-yl 251 2-MeO—C₆H₄ Me 2-Me- 1 imidazol-1-yl 252 3-MeO—C₆H₄ Me 2-Me- 1 imidazol-1-yl 253 4-MeO—C₆H₄ Me 2-Me- 1 imidazol-1-yl 254 2,5-Me₂—C₆H₃ Me 2-Me- 1 imidazol-1-yl 255 C₆H₅ Et 2-Me- 1 imidazol-1-yl 256 4-Cl—C₆H₄ Et 2-Me- 1 imidazol-1-yl 257 4-Me—C₆H₄ Et 2-Me- 1 imidazol-1-yl 258 C₆H₅ Allyl 2-Me- 1 imidazol-1-yl 259 4-Cl—C₆H₄ Allyl 2-Me- 1 imidazol-1-yl 260 4-Me—C₆H₄ Allyl 2-Me- 1 imidazol-1-yl 261 C₆H₅ Me 1H-1,2,4- 1 mp 86-87° C. Triazol-1-yl 262 2-F—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 263 3-F—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 264 4-F—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 265 2-Cl—C₆H₄ Me 1H-1,2,4- 1 mp 101.5-102.5° C. Triazol-1-yl 266 3-Cl—C₆H₄ Me 1H-1,2,4- 1 ¹H-NMR(CDCl₃) δ ppm: Triazol-1-yl 4.06(3H, s), 4.94(2H, s), 6.63- 7.65(8H, m), 7.96(1H, s), 9.12(1H, s) 267 4-Cl—C₆H₄ Me 1H-1,2,4- 1 mp 101-102° C. Triazol-1-yl 268 2-Me—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 269 3-Me—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 270 4-Me—C₆H₄ Me 1H-1,2,4- 1 mp 98.5-99.5° C. Triazol-1-yl 271 2-MeO—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 272 3-MeO—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 273 4-MeO—C₆H₄ Me 1H-1,2,4- 1 Triazol-1-yl 274 2,5-Me₂—C₆H₃ Me 1H-1,2,4- 1 mp 96° 98° C. Triazol-1-yl 275 C₆H₅ Et 1H-1,2,4- 1 mp 78.5-80.5° C. Triazol-1-yl 276 4-Cl—C₆H₄ Et 1H-1,2,4- 1 Triazol-1-yl 277 4-Me—C₆H₄ Et 1H-1,2,4- 1 Triazol-1-yl 278 C₆H₅ Allyl 1H-1,2,4- 1 ¹H-NMR(CDCl₃) δ ppm: 4.71- Triazol-1-yl 4.74(2H, m), 4.94(2H, s), 5.25- 5.37(2H, m), 5.91-6.06(1H, m), 6.76-7.59(9H, m), 7.96(1H, s), 9.13(1H, s) 279 4-Cl—C₆H₄ Allyl 1H-1,2,4- 1 Triazol-1-yl 280 4-Me—C₆H₄ Allyl 1H-1,2,4- 1 Triazol-1-yl 281 C₆H₅ Me Pyrazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.02(3H, s), 4.78(2H, s), 6.40(1H, dd, J=3.1, 1.8), 6.78- 7.62(10H, m), 8.42(1H, d, J=2.4) 282 2-F—C₆H₄ Me Pyrazol-1-yl 1 283 3-F—C₆H₄ Me Pyrazol-1-yl 1 284 4-F—C₆H₄ Me Pyrazol-1-yl 1 285 2-Cl—C₆H₄ Me Pyrazol-1-yl 1 mp 90-91° C. 286 3-Cl—C₆H₄ Me Prazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.26(3H, s), 4.78(2H, s), 6.42- 7.62(10H, m), 8.45(1H, d, J=2.4) 287 4-Cl—C₆H₄ Me Pyrazol-1-yl 1 mp 94-95° C. 288 2-Me—C₆H₄ Me Pyrazol-1-yl 1 289 3-Me—C₆H₄ Me Pyrazol-1-yl 1 290 4-Me—C₆H₄ Me Pyrazol-1-yl 1 mp 82-83° C. 291 2-Cl- Me Pyrazol-1-yl 1 mp 87.5-88.5° C. pyridin-3-yl 292 3-MeO—C₆H₄ Me Pyrazol-1-yl 1 293 4-MeO—C₆H₄ Me Pyrazol-1-yl 1 294 2,5-Me₂—C₆H₃ Me Pyrazol-1-yl 1 mp 78-80° C. 295 C₆H₅ Et Pyrazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 1.36(3H, t, J=6.7), 4.27(2H, q, J=6.7), 4.79(2H, s), 6.40- 7.61 (11H, m), 8.48(1H, d, J=3.1) 296 4-Cl—C₆H₄ Et Pyrazol-1-yl 1 297 4-Me—C₆H₄ Et Pyrazol-1-yl 1 298 C₆H₅ Allyl Pyrazol-1-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.69- 4.73(2H, m), 4.80(2H, s), 5.23- 5.38(2H, m), 5.96-6.10(1H, m), 6.40-7.62(11H, m), 8.48(1H, d, J=2.4) 299 4-Cl—C₆H₄ Allyl Pyrazol-1-yl 1 300 C₆H₅ Me Pyrazol-1-yl 0 ¹H-NMR(CDCl₃) δ ppm: 4.03(3H, s), 6.34(1H, t, J=2.9), 6.82-7.63(10H, m), 8.37(1H, d, J=2.9) 301 C₆H₅ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.06(3.99)(3H, s), 5.05(4.96)(2H, s), 6.73- 7.61(10H, m), 8.46(8.39)(1H, d, J=1.8) 302 2-F—C₆H₄ Me Isoxazol-3-yl 1 303 3-F—C₆H₄ Me Isoxazol-3-yl 1 304 4-F—C₆H₄ Me Isoxazol-3-yl 1 305 2-Cl—C₆H₄ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.08(4.01)(3H, s), 5.14(5.12)(2H, s), 6.76- 7.68(9H, m), 8.46(8.40)(1H, d, J=1.8) 306 3-Cl—C₆H₄ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.07(4.01)(3H, s), 5.04(4.95)(2H, s), 6.70- 7.56(9H, m), 8.48(8.40)(1H, d, J=1.8) 307 4-Cl—C₆H₄ Me Isoxazol-3-yl 1 4.06(3.99)(3H, s), 5.03(4.94)(3H, s), 6.72-7.56(9H, m), 8.47(8.39)(1H, d, J=1.8) 308 2-Br—C₆H₄ Me Isoxazol-3-yl 1 309 3-Br—C₆H₄ Me Isoxazol-3-yl 1 310 4-Br—C₆H₄ Me Isoxazol-3-yl 1 311 3-I—C₆H₄ Me Isoxazol-3-yl 1 312 2-Me—C₆H₄ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.20(2.17)(3H, s), 4.07(4.00)(3H, s), 5.03(4.97)(2H, s), 6.68- 7.64(9H, m), 8.44(8.39)(1H, d, J=1.8) 313 3-Me—C₆H₄ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.29(2.27)(3H, s), 4.07(4.00)(3H, s), 5.03(4.95)(2H, s), 6.62- 7.61(9H, m), 8.47(8.39)(1H, d, J=1.8) 314 4-Me—C₆H₄ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.25(3H, s), 4.06(3.99)(3H, s), 5.01(4.93)(2H, s), 6.70- 7.60(9H, m), 8.46(8.39)(1H, d, J=1.8) 315 2-Et—C₆H₄ Me Isoxazol-3-yl 1 316 3-Et—C₆H₄ Me Isoxazol-3-yl 1 317 4-Et—C₆H₄ Me Isoxazol-3-yl 1 318 2-MeO—C₆H₄ Me Isoxazol-3-yl 1 319 3-MeO—C₆H₄ Me Isoxazol-3-yl 1 320 4-MeO—C₆H₄ Me Isoxazol-3-yl 1 321 2-CF₃—C₆H₄ Me Isoxazol-3-yl 1 322 3-CF₃—C₆H₄ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.05(3.98)(3H, s), 5.10(5.01)(2H, s), 6.74(1H, d, J=1.8), 6.94-7.57(8H, m), 8.47(8.40)(1H, d, J=1.8) 323 4-CF₃—C₆H₄ Me Isoxazol-3-yl 1 324 2,4-F₂—C₆H₃ Me Isoxazol-3-yl 1 325 2,5-F₂—C₆H₃ Me Isoxazol-3-yl 1 326 2,6-F₂—C₆H₃ Me Isoxazol-3-yl 1 327 3,4-F₂—C₆H₃ Me Isoxazol-3-yl 1 328 3,5-F₂—C₆H₃ Me Isaxazol-3-yl 1 329 2,3-Cl₂—C₆H₃ Me Isoxazol-3-yl 1 330 2,4-Cl₂—C₆H₃ Me Isoxazol-3-yl 1 331 2,5-Cl₂—C₆H₃ Me Isoxazol-3-yl 1 332 3,4-Cl₂—C₆H₃ Me Isoxazol-3-yl 1 333 3,5-Cl₂—C₆H₃ Me Isoxazol-3-yl 1 334 2,3-Me₂—C₆H₃ Me Isoxazol-3-yl 1 335 2,4-Me₂—C₆H₃ Me Isoxazol-3-yl 1 336 2,5-Me₂—C₆H₃ Me Isoxazol-3-yl 1 mp 104-108° C. 337 3,4-Me₂—C₆H₃ Me Isoxazol-3-yl 1 338 3,5-Me₂—C₆H₃ Me Isoxazol-3-yl 1 339 2-Cl-4-Me—C₆H₃ Me Isoxazol-3-yl 1 340 2-Cl-5-Me—C₆H₃ Me Isoxazol-3-yl 1 341 4-Cl-2-Me—C₆H₃ Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.16(2.13)(3H, s), 4.07(3.99)(3H, s), 5.01 (4.95)(2H, s), 6.59- 7.58(8H, m), 8.45(8.40)(1H, d, J=1.8) 342 4-Cl-3-Me—C₆H₃ Me Isoxazol-3-yl 1 343 3-Ph—C₆H₄ Me Isoxazol-3-yl 1 344 4-Ph—C₆H₄ Me Isoxazol-3-yl 1 345 3-i-PrO—C₆H₄ Me Isoxazol-3-yl 1 346 3-i-Pr—C₆H₄ Me Isoxazol-3-yl 1 347 4-i-Pr—C₆H₄ Me Isoxazol-3-yl 1 348 3-t-Bu—C₆H₄ Me Isoxazol-3-yl 1 349 2-MeS—C₆H₄ Me Isoxazol-3-yl 1 350 4-MeS—C₆H₄ Me Isoxazol-3-yl 1 351 2,3,6-F₃—C₆H₂ Me Isoxazol-3-yl 1 352 2,4,5-Cl₃—C₆H₂ Me Isoxazol-3-yl 1 353 3-PhO—C₆H₄ Me Isoxazol-3-yl 1 354 3,4,5-(MeO)₃—C₆H₂ Me Isoxazol-3-yl 1 355 2,3,5-Me₃p13 C₆H₂ Me Isoxazol-3-yl 1 356 3,4,5-Me₃—C₆H₂ Me Isoxazol-3-yl 1 357 C₆F₅ Me Isoxazol-3-yl 1 358 4-Cl-3-Et—C₆H₃ Me Isoxazol-3-yl 1 359 3-EtO—C₆H₄ Me Isoxazol-3-yl 1 360 4-EtO—C₆H₄ Me Isoxazol-3-yl 1 361 C₆H₅ Me Isoxazol-3-yl 0 362 4-F—C₆H₄ Me Isoxazol-3-yl 0 363 3-Cl—C₆H₄ Me Isoxazol-3-yl 0 364 4-Cl—C₆H₄ Me Isoxazol-3-yl 0 365 3-Me—C₆H₄ Me Isoxazol-3-yl 0 366 4-Me—C₆H₄ Me Isoxazol-3-yl 0 367 4-Et—C₆H₄ Me Isoxazol-3-yl 0 368 4-NO₂—C₆H₄ Me Isoxazol-3-yl 0 369 3,4-C₂—C₆H₃ Me Isoxazol-3-yl 0 370 3,5-Cl₂—C₆H₃ Me Isoxazol-3-yl 0 371 3,4-Me₂—C₆H₃ Me Isoxazol-3-yl 0 372 3,5-Me₂—C₆H₃ Me Isoxazol-3-yl 0 373 3-PhO—C₆H₄ Me Isoxazol-3-yl 0 374 4-Cl-3-Et—C₆H₃ Me Isoxazol-3-yl 0 375 3-EtO—C₆H₄ Me Isoxazol-3-yl 0 376 3-CF₃—C₆H₄ Me Isoxazol-3-yl 0 377 4-CF₃—C₆H₄ Me Isoxazol-3-yl 0 378 3-i-PrO—C₆H₄ Me Isoxazol-3-yl 0 379 3-i-Pr—C₆H₄ Me Isoxazol-3-yl 0 380 4-Cl-3-Me—C₆H₃ Me Isoxazol-3-yl 0 381 pyridin-2-yl Me Isoxazol-3-yl 1 382 pyridin-3-yl Me Isoxazol-3-yl 1 383 5-Cl- Me Isoxazol-3-yl 1 pyridin-2-yl 384 3-Cl- Me Isoxazol-3-yl 1 pyridin-2-yl 385 6-Cl- Me Isoxazol-3-yl 1 pyridin-2-yl 386 2-Cl- Me Isoxazol-3-yl 1 pyridin-3-yl 387 5-CF₃- Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: pyridin-2-yl 3.98(3H. s), 5.32(2H, s), 6.63(1H, d, J=8.5), 6.73(1H, d, J=1.8), 7.27-7.71(5H, m), 8.30(1H; s), 8.39(1 H, d, J=1.8) 388 3-CF₃- Me Isoxazol-3-yl 1 mp 125-126.5° C. pyridin-2-yl 389 6-CF₃-3-Cl- Me Isoxazol-3-yl 1 pyridin-2-yl 390 5-CF-3-Cl- Me Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ pyridin-2-yl ppm: 4.00(3H, s), 5.41(2H, s), 6.76(1H, d, J=1.8), 7.27- 7.78(5H, m), 8.15(1H, s), 8.46(1H, d, J=1.8) 391 Benzothiazol- Me Isoxazol-3-yl 1 2-yl 392 Benzoxazol- Me Isoxazol-3-yl 1 2-yl 393 Quinolin-2-yl Me Isoxazol-3-yl 1 394 5-CF₃-1,3,4- Me Isoxazol-3-yl 1 thiadiazol-2-yl 395 pyrimidin-2-yl Me Isoxazol-3-yl 1 396 5-Cl-6-Me- Me Isoxazol-3-yl 1 pyrimidin-4-yl 397 5-Et-6-Me- Me Isoxazol-3-yl 1 pyrimidin-4-yl 398 6-Cl- Me Isoxazol-3-yl 1 pyrazin-2-yl 399 3,6-Me₂- Me Isoxazol-3-yl 1 pyrazin-2-yl 400 5-Me- Me Isoxazol-3-yl 1 Isoxazol-3-yl 401 C₆H₅ Me 5-Me- 1 2.43(3H, s), 3.97(4.04)(3H, s), isoxazol-3-yl 4.96(5.06)(2H, s), 6.35(6.55)(1H, s), 6.83- 7.60(9H, m) 402 2-F—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 403 3-F—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 404 4-F—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 405 2-Cl—C₆H₄ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: isoxazol-3-yl 2.44(3H, s), 4.07(3.98)(3H, s), 5.15(5.06)(2H, s), 6.38( 6.57)(1H, s), 6.78-7.66(8H, m) 406 3-Cl—C₆H₄ Me 5-Me- 1 mp 111.0-123.0° C. isoxazol-3-yl 407 4-Cl—C₆H₄ Me 5-Me- 1 mp 74.0-85.0° C. isoxazol-3-yl 408 2-Br—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 409 3-Br—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 410 4-Br—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 411 3-I—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 412 2-Me—C₆H₄ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: isoxazol-3-yl 2.20(2.22)(3H, s), 2.42(2.42)(3H, s), 3.98(4.06)(3H, s), 4.97(5.04)(2H, s), 6.35(6.53)(1H, s), 6.69- 7.63(8H, m) 413 3-Me—C₆H₄ Me 5-Me- 1 mp 92.0-93.0° C. isoxazol-3-yl 414 4-Me—C₆H₄ Me 5-Me- 1 mp 104.0-105.5° C. isoxazol-3-yl 415 2-Et—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 416 3-Et—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 417 4-Et—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 418 2-MeO—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 419 3-MeO—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 420 4-MeO—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 421 2-CF₃—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 422 3-CF₃—C₆H₄ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: isoxazol-3-yl 2.43(2.44)(3H, s), 4.03(3.97)(3H, s), 5.00(5.09)(2H, s), 6.35(1H, s), 6,56(6.57)(1H, s), 7.00- 7.64(7H, m) 423 4-CF₃—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 424 2,4-F₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 425 2,5-F₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 426 2,6-F₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 427 3,4-F₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 428 3,5-F₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 429 2,3-Cl₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 430 2,4-Cl₂C₆H₃ Me 5-Me- 1 isoxazol-3-yl 431 2,5-Cl₂-C₆H₃ Me 5-Me- 1 isoxazol-3-yl 432 3,4-Cl₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 433 3,5-Cl₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 434 2,3-Me₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 435 2,4-Me₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 436 2,5-Me₂—C₆H₃ Me 5-Me- 1 ¹H-NMR(CDCl₃) δ ppm: isoxazol-3-yl 2.15(2.16)(3H, s), 2.24(2.25)(3H, s), 2.42(2.43)(3H, s), 3.99(4.07)(3H, s), 4.95(5.01)(2H, s), 6.36- 7.64(8H, m) 437 3,4-Me₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 438 3,5-Me₂—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 439 2-Cl-4-Me—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 440 2-Cl-5-Me—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 441 4-Cl-2-Me—C₆H₃ Me 5-Me- 1 mp 79-83° C. isoxazol-3-yl 442 4-Cl-3-Me—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 443 3-Ph—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 444 4-Ph—C₆H₄ Me 5-Me- 1 mp 105.0-115.° C. isoxazol-3-yl 445 3-i-PrO—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 446 3-i-Pr—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 447 4-i-Pr—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 448 3-t-Bu—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 449 2-MeS—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 450 4-MeS—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 451 2,3,6-F_(3—C) ₆H₂ Me 5-Me- 1 isoxazol-3-yl 452 2,4,5-Cl₃—₆H₂ Me 5-Me- 1 isoxazol-3-yl 453 3-PhO—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 454 3,4,5-(MeO)₃—C₆H₂ Me 5-Me- 1 isoxazol-3-yl 455 2.3.5-(Me₃—C₆H₂ Me 5-Me- 1 isoxazol-3-yl 456 3,4,5-Me₃—C₆H₂ Me 5-Me- 1 isoxazol-3-yl 457 C₆F₅ Me 5-Me- 1 isoxazol-3-yl 458 4-Cl-3-Et—C₆H₃ Me 5-Me- 1 isoxazol-3-yl 459 3-EtO—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 460 4-EtO—C₆H₄ Me 5-Me- 1 isoxazol-3-yl 461 C₆H₅ Me 5-Me- 0 isoxazol-3-yl 462 4-F—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 463 3-Cl—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 464 4-Cl—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 465 3-Me—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 466 4-Me—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 467 4-Et—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 468 4-NO₂—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 469 3,4-Cl₂—C₆H₃ Me 5-Me- 0 isoxazol-3-yl 470 3,5-Cl₂—C₆H₃ Me 5-Me- 0 isoxazol-3-yl 471 3,4-Me₂—C₆H₃ Me 5-Me- 0 isoxazol-3-yl 472 3,5-Me₂—C₆H₃ Me 5-Me- 0 isoxazol-3-yl 473 3-PhO—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 474 4-Cl-3-Et—C₆H₃ Me 5-Me- 0 isoxazol-3-yl 475 3-EtO—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 476 3-CF₃—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 477 4-CF₃—C₆H₄ Me 5-Me- 0 isaxazol-3-yl 478 3-i-PrO—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 479 3-i-Pr—C₆H₄ Me 5-Me- 0 isoxazol-3-yl 480 4-Cl-3-Me—C₆H₃ Me 5-Me- 0 isoxazol-3-yl 481 Pyridin-2-yl Me 5-Me- 1 isoxazol-3-yl 482 Pyridin-3-yl Me 5-Me- 1 isoxazol-3-yl 483 5-Cl- Me 5-Me- 1 pyridin-2-yl isoxazol-3-yl 484 3-Cl- Me 5-Me- 1 ¹H-NMR(CDCl₃) δ pyridin-2-yl isoxazol-3-yl ppm: 2.42(3H, s), 3.97(3H, s), 5.35(2H, s), 6.35(1H, s), 6.76- 6.81(1H, m), 7.24-7.93(6H, m). 485 6-Cl- Me 5-Me- 1 pyridin-2-yl isoxazol-3-yl 486 2-Cl- Me 5-Me- 1 pyridin-3-yl isoxazol-3-yl 487 5-CF₃- Me 5-Me- 1 ¹H-NMR(CDCL₃) δ pyridin-2-yl isoxazol-3-yl ppm: 2.43(3H, s), 3.96(3H, s), 5.32(2H, s), 6.34(1H, d, J=1.2), 6.67(1 H, d, J=8.5), 7.24-7.72(5H, m), 8.31(1H, s) 488 3-CF₃- Me 5-Me- 1 pyridin-2-yl isoxazol-3-yl 489 6-CF₃-3-Cl- Me 5-Me- 1 pyridin-2-yl isoxazol-3-yl 490 5-CF₃-3-Cl- Me 5-Me- 1 ¹H-NMR(CDCl₃) δ pyridin-2-yl isoxazol-3-yl ppm:2.43(3H, s), 3.97(3H, s), 5.40(2H, s), 6.37(1H, s), 7.25- 8.17(6H, m). 491 Benzothiazol- Me 5-Me- 1 2-yl isoxazol-3-yl 492 Benzoxazol- Me 5-Me- 1 2-yl isoxazol-3-yl 493 Quinolin-2-yl Me 5-Me- 1 isoxazol-3-yl 494 5-CF₃-1,3,4- Me 5-Me- 1 thiadiazol-2-yl isoxazol-3-yl 495 Pyrimidin-2-yl Me 5-Me- 1 isoxazol-3-yl 496 5-Cl-6-Me- Me 5-Me- 1 pyrimidin-4-yl isoxazol-3-yl 497 5-Et-6-Me- Me 5-Me- 1 pyrimidin-4-yl isoxazol-3-yl 498 6-Cl- Me 5-Me- 1 pyrazin-2-yl isoxazol-3-yl 499 3,6-Me₂- Me 5-Me- 1 pyrazin-2-yl isoxazol-3-yl 500 5-Me- Me 5-Me- 1 isoxazol-3-yl isoxazol-3-yl 501 C₆H₅ Me Isoxazol-5-yl 1 502 2-F—C₆H₄ Me Isoxazol-5-yl 1 503 3-F—C₆H₄ Me Isoxazol-5-yl 1 504 4-F—C₆H₄ Me Isoxazol-5-yl 1 505 2-Cl—C₆H₄ Me Isoxazol-5-yl 1 506 3-Cl—C₆H₄ Me Isoxazol-5-yl 1 507 4-Cl—C₆H₄ Me Isoxazol-5-yl 1 Isomer A: ¹H-NMR(CDCl₃) δ ppm: 4.11(3H, s), 4.99(2H, s), 6.68-6.73(2H, m), 7.11(1H, d, J=1.8), 7.14-7.18(2H, m), 7.40-7.57(4H, m), 8.34(1H, d, J=1.8) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 4.03(3H, s), 4.92(2H, s), 6.21(1H, d, J=1.8), 6.68- 6.74(2H, m), 7.13-7.23(3H, m), 7.41-7.61(3H, m), 8.24(1H, d, J=1.8) 508 2-Br—C₆H₄ Me Isoxazol-5-yl 1 509 3-Br—C₆H₄ Me Isoxazol-5-yl 1 510 4-Br—C₆H₄ Me Isoxazol-5-yl 1 511 3-I—C₆H₄ Me Isoxazol-5-yl 1 512 2-Me—C₆H₄ Me Isoxazol-5-yl 1 Isomer A: mp 7l.5-72.5° C. Isomer B: mp 68.0-69.0° C. 513 3-Me—C₆H₄ Me Isoxazol-5-yl 1 514 4-Me—C₆H₄ Me Isoxazol-5-yl 1 515 2-Et—C₆H₄ Me Isoxazol-5-yl 1 516 3-Et—C₆H₄ Me Isoxazol-5-yl 1 517 4-Et—C₆H₄ Me Isoxazol-5-yl 1 518 2-MeO—C₆H₄ Me Isoxazol-5-yl 1 519 3-MeO—C₆H₄ Me Isoxazol-5-yl 1 520 4-MeO—C₆H₄ Me Isoxazol-5-yl 1 521 2-CF₃—C₆H₄ Me Isoxazol-5-yl 1 522 3-CF₃—C₆H₄ Me Isoxazol-5-yl 1 Isomer A: ¹H-NMR(CDCl₃) δ ppm: 4.10(3H, s), 5.07(2H, s), 6.91-7.02(2H, m), 7.11(1H, d, J=1.8), 7.15-7.59(6H, m), 8.34(1H, d, J=1.8) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 4.03(3H, s), 4.99(2H, s), 6.22(1H, d, J=1.8), 6.92- 7.62(8H, m), 8.24(1H, d, J=1.8) 523 4-CF₃—C₆H₄ Me Isoxazol-5-yl 1 524 2,4-F₂—C₆H₃ Me Isoxazol-5-yl 1 525 2,5-F₂—C₆H₃ Me Isoxazol-5-yl 1 526 2,6-F₂—C₆H₃ Me Isaxazol-5-yl 1 527 3,4-F₂—C₆H₃ Me Isoxazol-5-yl 1 528 3,5-F₂—C₆H₃ Me Isoxazol-5-yl 1 529 2,3-Cl₂—C₆H₃ Me Isoxazol-5-yl 1 530 2,4-Cl₂—C₆H₃ Me Isoxazol-5-yl 1 531 2,5-Cl₂—C₆H₃ Me Isoxazol-5-yl 1 532 3,4-Cl₂—C₆H₃ Me Isoxazol-5-yl 1 533 3,5-Cl₂—C₆H₃ Me Isoxazol-5-yl 1 534 2,3-Me₂—C₆H₃ Me Isoxazol-5-yl 1 535 2,4-Me₂—C₆H₃ Me Isoxazol-5-yl 1 536 2,5-Me₂—C₆H₃ Me Isoxazol-5-yl 1 Isomer A: mp 137.5-138.5° C. Isomer B: mp 93.0-94.5° C. 537 3,4-Me₂—C₆H₃ Me Isoxazol-5-yl 1 538 3,5-Me₂—C₆H₃ Me Isoxazol-5-yl 1 539 2-Cl-4-Mep—C₆H₃ Me Isoxazol-5-yl 1 540 2-Cl-5-Me—C₆H₃ Me Isoxazol-5-yl 1 541 4-Cl-2-Me—C₆H₃ Me Isoxazol-5-yl 1 Isomer A: mp 84.0-85.0° C. Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.16(3H, s), 4.04(3H, s), 4.93(2H, s), 6.20(1H, d, J=1.8), 6.62(1H, d, J=8.5), 6.99-7.63(6H, m), 8.22(1H, d, J=1.8) 542 4-Cl-3-Me—C₆H₃ Me Isoxazol-5-yl 1 543 3-Ph—C₆H₄ Me Isoxazol-5-yl 1 544 4-Ph—C₆H₄ Me Isoxazol-5-yl 1 545 3-i-PrO—C₆H₄ Me Isoxazol-5-yl 1 546 3-i-Pr—C₆H₄ Me Isoxazol-5-yl 1 547 4-i-Pr—C₆H₄ Me Isoxazol-5-yl 1 548 3-t-Bu—C₆H₄ Me Isoxazol-5-yl 1 549 2-MeS—C₆H₄ Me Isoxazol-5-yl 1 550 4-MeS—C₆H₄ Me Isoxazol-5-yl 1 551 2,3,6-F₃—C₆H₂ Me Isoxazol-5-yl 1 552 2,4,5-Cl₃—C₆H₂ Me Isoxazol-5-yl 1 553 3-PhO—C₆H₄ Me Isoxazol-5-yl 1 554 3,4,5-(MeO)₃—C₆H₂ Me Isoxazol-5-yl 1 555 2,3,5-Me_(3—C) ₆H₂ Me Isoxazol-5-yl 1 556 3,4,5-Me₃—C₆H₂ Me Isoxazol-5-yl 1 557 C₆F₅ Me Isoxazol-5-yl 1 558 4-Cl-3-Et—C₆H₃ Me Isoxazol-5-yl 1 559 3-EtO—C₆H₄ Me Isaxazol-5-yl 1 560 4-EtO—C₆H₄ Me Isoxazol-5-yl 1 561 C₆H₅ Me Isoxazol-5-yl 0 562 4-F—C₆H₄ Me Isoxazol-5-yl 0 563 3-Cl—C₆H₄ Me Isoxazol-5-yl 0 564 4-Cl—C₆H₄ Me Isoxazol-5-yl 0 565 3-Me—C₆H₄ Me Isoxazol-5-yl 0 566 4-Me—C₆H₄ Me Isoxazol-5-yl 0 567 4-Et—C₆H₄ Me Isoxazol-5-yl 0 568 4-NO₂—C₆H₄ Me Isoxazol-5-yl 0 569 3,4-Cl₂—C₆H₃ Me Isoxazol-5-yl 0 570 3,5-Cl₂—C₆H₃ Me Isoxazol-5-yl 0 571 3,4-Me₂—C₆H₃ Me Isoxazol-5-yl 0 572 3,5-Me₂—C₆H₃ Me Isoxazol-5-yl 0 573 3-PhO—C₆H₄ Me Isoxazol-5-yl 0 574 4-Cl-3-Et—C₆H₃ Me Isoxazol-5-yl 0 575 3-EtO—C₆H₄ Me Isoxazol-5-yl 0 576 3-CF₃—C₆H₄ Me Isoxazol-5-yl 0 577 4-CF₃—C₆H₄ Me Isoxazol-5-yl 0 578 3-i-PrO—C₆H₄ Me Isoxazol-5-yl 0 579 3-i-Pr—C₆H₄ Me Isoxazol-5-yl 0 580 4-Cl-3-Me—C₆H Me Isoxazol-5-yl 0 581 Pyridin-2-yl Me Isoxazol-5-yl 1 582 Pyridin-3-yl Me Isoxazol-5-yl 1 583 5-Cl- Me Isoxazol-5-yl 1 pyridin-2-yl 584 3-Cl- Me Isoxazol-5-yl 1 pyridin-2-yl 585 6-Cl- Me Isoxazol-5-yl 1 pyridin-2-yl 586 2-Cl- Me Isoxazol-5-yl 1 pyridin-3-yl 587 5-CF₃- Me Isoxazol-5-yl 1 pyridin-2-yl 588 3-CF₃- Me Isoxazol-5-yl 1 pyridin-2-yl 589 6-CF₃-3-Cl- Me Isoxazol-5-yl 1 pyridin-2-yl 590 5-CF₃-3-Cl- Me isoxazol-5-yl 1 pyridin-2-yl 591 Benzothiazol- Me Isoxazol-5-yl 1 2-yl 592 Benzoxazol- Me Isoxazol-5-yl 1 2-yl 593 Quinolin-2-yl Me Isoxazol-5-yl 1 594 5-CF₃-1,3,4- Me Isoxazol-5-yl 1 thiadiazol-2-yl 595 Pyrimidin-2-yl Me Isoxazol-5-yl 1 596 5-Cl-6-Me- Me Isoxazol-5-yl 1 pyrimidin-4-yl 597 5-Et-6-Me- Me Isoxazol-5-yl 1 pyrimidin-4-yl 598 6-Cl- Me Isoxazol-5-yl 1 Pyrazin-2-yl 599 3,6-Me₂- Me Isoxazol-5-yl 1 Pyrazin-2-yl 600 5-Me- Me Isoxazol-5-yl 1 isoxazol-3-yl 601 C₆H₅ Me 3-Me- 1 Isomer A: mp 99.0-100.0° C. isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.27(3H, s), 4.02(3H, s), 4.95(2H, s), 5.99(1H, s), 6.80- 7.65(9H, m) 602 2-F—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 603 3-F—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 604 4-F—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 605 2-Cl—C₆H₄ Me 3-Me- 1 Isomer A: mp 87.0-88.0° C. isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.27(3H, s), 4.04(3H, s), 5.01(2H, s), 6.02(1H, s), 6.81- 7.74(8H, m) 606 3-Cl—C₆H₄ Me 3-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ isoxazol-5-yl ppm: 2.35(3H, s), 4.10(3H, s), 5.00(2H, s), 6.66-6.91(3H, m), 6.94(1H, s), 7.10-7.57(5H, m). Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.28(3H, s), 4.03(3H, s), 4.94(2H, s), 6.01(1H, s), 6.68- 7.65(8H, m) 607 4-Cl-C₆H₄ Me 3-Me- 1 Isomer A: mp 110.0-111.0° C. isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.27(3H, s), 4.01(3H, s), 4.92(2H, s), 5.99(1H, s), 6.71- 7.60(8H, m) 608 2-Br—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 609 3-Br—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 610 4-Br—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 611 3-I—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 612 2-Me—C₆H₄ Me 3-Me- 1 Isomer A: mp 80.0-81.0° C. isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.17(3H, s), 2.26(3H, s), 4.03(3H, s), 4.93(2H, s), 5.98(1H, s), 6.71-7.68(8H, m) 613 3-Me—C₆H₄ Me 3-Me- 1 Isomer A: mp 109.0-110.0° C. isoxazol-5-yl Isomer B: mp 94.5-95.5° C. 614 4-Me—C₆H₄ Me 3-Me- 1 Isomer A: mp 126.0-127.0° C. isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.25(3H, s), 2.27(3H, s), 4.02(3H, s), 4.92(2H, s), 5.99(1H, s), 6.70-7.64(8H, m) 615 2-Et—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 616 3-Et—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 617 4-Et—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 618 2-MeO—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 619 3-MeO—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 620 4-MeO—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 621 2-CF₃—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 622 3-CF₃—C₆H₄ Me 3-Me- 1 Isomer A: ¹H-NMR(CDCl₃) δ isoxazol-5-yl ppm: 2.34(3H, s), 4.08(3H, s), 5.05(2H, s), 6.92(1H, s), 6.94- 7.57(8H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.27(3H, s), 4.02(3H, s), 4.99(2H, s), 6.01(1H, s), 6.96- 7.61 (8H, m) 623 4-CF₃—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 624 2,4-F₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 625 2,5-F₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 626 2,6-F₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 627 3,4-F₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 628 3,5-F₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 629 2,3-Cl₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 630 2,4-Cl₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 631 2,5-Cl₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 632 3,4-Cl₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 633 3,5-Cl₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 634 2,3-Me₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 635 2,4-Me₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 636 2,5-Me₂—C₆H₃ Me 3-Me- 1 Isomer A mp 113-114° C. isoxazol-5-yl Isomer B mp 107-108° C. 637 3,4-Me₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 638 3,5-Me₂—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 639 2-Cl-4-Me—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 640 2-Cl-5-Me—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 641 4-Cl-2-Me—C₆H₃ Me 3-Me- 1 Isomer A: mp 76.5-77.5° C. isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.12(3H, s), 2.26(3H, s), 4.03(3H, s), 4.93(2H, s), 5.97(1H, s), 6.62(1H, d, J=8.5), 6.99-7.62(6H, m) 642 4-Cl-3-Me—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 643 3-Ph—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 644 4-Ph—C₆H₄ Me 3-Me- 1 Isomer A: mp 130.5-131.5° C. isoxazol-5-yl Isomer B: mp 102.5-103.5° C. 645 3-i-PrO—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 646 3-i-Pr—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 647 4-i-Pr—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 648 3-t-Bu—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 649 2-MeS—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 650 4-MeS—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 651 2,3,6-F₃—C₆H₂ Me 3-Me- 1 isoxazol-5-yl 652 2,4,5-Cl₃—C₆H₂ Me 3-Me- 1 isoxazol-5-yl 653 3-PhO—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 654 3,4,5-(MeO)₃—C₆H₂ Me 3-Me- 1 isoxazol-5-yl 655 2,3,5-Me₃—C₆H₂ Me 3-Me- 1 isoxazol-5-yl 656 3,4,5-Me₃—C₆H₂ Me 3-Me- 1 isoxazol-5-yl 657 C₆F₅ Me 3-Me- 1 isoxazol-5-yl 658 4-Cl-3-Et—C₆H₃ Me 3-Me- 1 isoxazol-5-yl 659 3-EtO—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 660 4-EtO—C₆H₄ Me 3-Me- 1 isoxazol-5-yl 661 C₆H₅ Me 3-Me- 0 Isomer A: mp 100.0-105.5° C. isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.28(3H, s), 3.94(3H, s), 6.17(1H, s), 6.92-7.41(9H, m) 662 4-F—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 663 3-Cl—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 0 664 4-Cl—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 665 3-Me—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 666 4-Me—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 667 4-Et—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 668 4-NO₂—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 669 3,4-Cl₂—C₆H₃ Me 3-Me- 0 isoxazol-5-yl 670 3,5-Cl₂—C₆H₃ Me 3-Me- 0 isoxazol-5-yl 671 3,4-Me₂—C₆H₃ Me 3-Me- 0 isoxazol-5-yl 672 3,5-Me₂—C₆H₃ Me 3-Me- 0 isoxazol-5-yl 673 3-PhO—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 674 4-Cl-3-Et—C₆H₃ Me 3-Me- 0 isoxazol-5-yl 675 3-EtO—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 676 3-CF₃—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 677 4-CF₃—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 678 3-i-PrO—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 679 3-i-Pr—C₆H₄ Me 3-Me- 0 isoxazol-5-yl 680 4-Cl-3-Me—C₆H₃ Me 3-Me- 0 isoxazol-5-yl 681 Pyridin-2-yl Me 3-Me- 1 isoxazol-5-yl 682 Pyridin-3-yl Me 3-Me- 1 isoxazol-5-yl 683 5-Cl- Me 3-Me- 1 pyridin-2-yl isoxazol-5-yl 684 3-Cl- Me 3-Me- 1 pyridin-2-yl isoxazol-5-yl 685 6-Cl- Me 3-Me- 1 pyridin-2-yl isoxazol-5-yl 686 2-Cl- Me 3-Me- 1 pyridin-3-yl isoxazol-5-yl 687 5-CF₃- Me 3-Me- 1 Isomer A: mp 88.0-90.0° C. pyridin-2-yl isoxazol-5-yl Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.28(3H, s), 4.01(3H, s), 5.32(2H, s), 6.00(1H, s), 6.64(1H, d, J=9.2),7.22- 7.73(5H, m), 8.30(1H, d, J=1.2) 688 3-CF₃- Me 3-Me- 1 pyridin-2-yl isoxazol-5-yl 689 6-CF₃-3-Cl- Me 3-Me- 1 pyridin-2-yl isoxazol-5-yl 690 5-CF₃-3-Cl- Me 3-Me- 1 Isomer A: mp 77.0-79.0° C. pyridin-2-yl isaxazol-5-yl Isomer B: ¹H-NMR(CDCL₃) δ ppm: 2.27(3H, s), 4.03(3H, s), 5.39(2H, s), 6.02(1H, s), 7.22- 7.67(4H, m), 7.79(1H, d, J=1.8), 8.17(1H, d, J=1.8) 691 Benzothiazol- Me 3-Me- 1 2-yl isoxazol-5-yl 692 Benzoxazol- Me 3-Me- 1 2-yl isoxazol-5-yl 693 Quinolin-2-yl Me 3-Me- 1 isoxazol-5-yl 694 5-CF₃-1,3,4- Me 3-Me- 1 thiadiazol-2-yl isoxazol-5-yl 695 Pyrimidin-2-yl Me 3-Me- 1 isoxazol-5-yl 696 5-Cl-6-Me- Me 3-Me- 1 pyrimidin-4-yl isoxazol-5-yl 697 5-Et-6-Me- Me 3-Me- 1 pyrimidin-4-yl isoxazol-5-yl 698 6-Cl- Me 3-Me- 1 pyrazin-2-yl isoxazol-5-yl 699 3,6-Me₂- Me 3-Me- 1 pyrazin-2-yl isoxazol-5-yl 700 5-Me- Me 3-Me- 1 isoxazol-3-yl isoxazol-5-yl 701 C₆H₅ Me 1,3,4-Oxadiazol-2-yl 1 mp 88.0-89.0° C. 702 2-F—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 703 3-F—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 704 4-F—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 705 2-Cl—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 mp l20.0-121.0° C. 706 3-Cl—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 mp 97.0-98.0° C. 707 4-Cl—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 mp 120-122° C. 708 2-Br—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 709 3-Br—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 710 4-Br—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 711 3-I—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 712 2-Me—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 mp 95-96.5° C. 713 3-Me—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 mp 78.5-79.5° C. 714 4-Me—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 715 2-Et—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 716 3-Et—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 ¹H-NMR(CDCl₃) δ ppm: 1.14(3H, t, J=7.3), 2.56(2H, q, J=7.3), 4.08(3H, s), 4.99(2H, s), 6.73-7.65(8H, m), 8.43(1H, s) 717 4-Et—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 718 2-MeO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 mp 85.0-86.5° C. 719 3-MeO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 720 4-MeO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 721 2-CF₃—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 722 3-CF₃—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.06(3H, s), 5.03(2H, s), 6.92- 7.59(8H, m), 8.44(1H, s) 723 4-CF₃—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 724 2,4-F₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 725 2,5-F₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 726 2,6-F₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 727 3,4-F₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 728 3,5-F₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 729 2,3-Cl₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 730 2,4-Cl₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 731 2,5-Cl₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 mp 152.0-153.0° C. 732 3,4-Cl₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.08(3H, s), 4.96(2H, s), 6.63(1H, dd, J=2.4, 8.5), 6.89(1H, d, J=3.1), 7.24- 7.57(5H, m), 8.46(1H, s) 733 3,5-Cl₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 734 2,3-Me₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 735 2,4-Me₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 736 2,5-Me₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 mp 134-135° C. 737 3,4-Me₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 738 3,5-Me₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 739 2-Cl-4-Me—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 740 2-Cl-5-Me—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 741 4-Cl-2-Me—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 mp 85.5-86.5° C. 742 4-Cl-3-Me—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 743 3-Ph—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 744 4-Ph—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 745 3-i-PrO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 746 3-i-Pr—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 747 4-i-Pr—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 748 3-t-Bu—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 749 2-MeS—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 750 4-MeS—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 751 2,3,6-F₃—C₆H₂ Me 1,3,4-Oxadiazol-2-yl 1 752 2,4,5-Cl₃—C₆H₂ Me 1,3,4-Oxadiazol-2-yl 1 753 3-PhO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 754 3,4,5-(MeO)₃—C₆H₂ Me 1,3,4-Oxadiazol-2-yl 1 755 2,3,5-Me₃—C₆H₂ Me 1,3,4-Oxadiazol-2-yl 1 756 3,4,5-Me₃—C₆H₂ Me 1,3,4-Oxadiazol-2-yl 1 757 C₆F₅ Me 1,3,4-Oxadiazol-2-yl 1 758 4-Cl-3-Et—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 1 759 3-EtO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 760 4-EtO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 1 761 C₆H₅ Me 1,3,4-Oxadiazol-2-yl 0 762 4-F—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 763 3-Cl—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 764 4-Cl—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 765 3-Me—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 766 4-Me—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 767 4-Et—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 768 4-NO₂—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 769 3,4-Cl₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 0 770 3,5-Cl₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 0 771 3,4-Me₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 0 772 3,5-Me₂—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 0 773 3-PhO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 774 4-Cl-3-Et—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 0 775 3-EtO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 776 3-CF₃—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 777 4-CF₃—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 778 3-i-PrO—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 779 3-i-Pr—C₆H₄ Me 1,3,4-Oxadiazol-2-yl 0 780 4Cl-3-Me—C₆H₃ Me 1,3,4-Oxadiazol-2-yl 0 781 Pyridin-2-yl Me 1,3,4-Oxadiazol-2-yl 1 782 Pyridin-3-yl Me 1,3,4-Oxadiazol-2-yl 1 783 5-Cl- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-2-yl 784 3-Cl- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-2-yl 785 6-Cl- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-2-yl 786 2-Cl- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-3-yl 787 5-CF₃- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-2-yl 788 3-CF₃- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-2-yl 789 6-CF₃-3-Cl- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-2-yl 790 5-CF₃-3-Cl- Me 1,3,4-Oxadiazol-2-yl 1 pyridin-2-yl 791 Benzothiazol- Me 1,3,4-Oxadiazol-2-yl 1 2-yl 792 Benzoxazol- Me 1,3,4-Oxadiazol-2-yl 1 -2-yl 793 Quinolin-2-yl Me 1,3,4-Oxadiazol-2-yl 1 794 5-CF₃-1,3,4- Me 1,3,4-Oxadiazol-2-yl 1 thiadiazol-2-yl 795 Pyrimidin-2-yl Me 1,3,4-Oxadiazol-2-yl 1 796 5-Cl-6-Me- Me 1,3,4-Oxadiazol-2-yl 1 pyrimidin-4-yl Me 797 5-Et-6-Me- Me 1,3,4-Oxadiazol-2-yl 1 pyrimidin-4-yl 798 6-Cl- Me 1,3,4-Oxadiazol-2-yl 1 pyrazin-2-yl 799 3,6-Me₂- Me 1,3,4-Oxadiazol-2-yl 1 pyrazin-2-yl 800 5-Me- Me 1,3,4-Oxadiazol-2-yl 1 isoxazol-3-yl 801 C₆H₅ Me 1,2,4-Oxadiazol-3-yl 1 mp 70.5-71.5° C. 802 2-F—C₆H₄ Me 1,2,4-Oxadiazoi-3-yl 1 803 3-F—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 804 4-F—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 805 2-Cl—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 mp 139.0-140.0° C. 806 3-Cl—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 807 4-Cl—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 mp 107-108° C. 808 2-Br—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 809 3-Br—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 810 4-Br—C₆H₄ Me 1,2.4-Oxadiazol-3-yl 1 811 3-I—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 812 2-Me—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 mp 79-80° C. 813 3-Me—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 814 4-Me—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 mp 92.5-93.5° C. 815 2-Et—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 816 3-Et—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 817 4-Et—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 818 2-MeO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 819 3-MeO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 820 4-MeO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 821 2-CF₃—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 822 3-CF₃—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 823 4-CF₃—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 824 2,4-F₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 825 2,5-F₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 826 2,6-F₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 827 3,4-F₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 828 3,5-F₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 829 2,3-Cl₂—C₆H₃ Me 1 ,2,4-Oxadiazol-3-yl 1 830 2,4-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 831 2,5-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 832 3,4-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 833 3,5-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 834 2,3-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 835 2,4-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 836 2,5-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 Isomer A: mp 116.5-117.5° C. Isomer B: mp 69-71° C. 837 3,4-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 838 3,5-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 839 2-Cl-4-Me—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 840 2-Cl-5-Me—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 841 4-Cl-2-Me—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 mp 127-128° C. 842 4-Cl-3-Me—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 843 3-Ph—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 844 4-Ph—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 mp 147.5-148.5° C. 845 3-i-PrO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 846 3-i-Pr—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 847 4-i-Pr—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 848 3-t-Bu—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 849 2-MeS—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 850 4-MeS—C₆H₄ Me 1,2,4-Oxadiazal-3-yl 1 851 2,3,6-F₃—C₆H₂ Me 1,2,4-Oxadiazol-3-yl 1 852 2,4,5-Cl₃—C₆H₂ Me 1,2,4-Oxadiazol-3-yl 1 853 3-PhO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 854 3,4,5-(MeO)₃—C₆H₂ Me 1,2,4-Oxadiazol-3-yl 1 855 2,3,5-Me₃—C₆H₂ Me 1,2,4-Oxadiazol-3-yl 1 856 3,4,5-Me₃—C₆H₂ Me 1,2,4-Oxadiazol-3-yl 1 857 C₆F₅ Me 1,2,4-Oxadiazol-3-yl 1 858 4-Cl-3-Et—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 1 859 3-EtO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 860 4-EtO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 1 861 C₆H₅ Me 1,2,4-Oxadiazol-3-yl 0 862 4-F—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 863 3-Cl—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 864 4-Cl—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 865 3-Me—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 866 4-Me—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 867 4-Et—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 868 4-NO₂—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 869 3,4-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 0 870 3,5-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 0 871 3,4-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 0 872 3,5-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 0 873 3-PhO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 874 4-Cl-3-Et—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 0 875 3-EtO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 876 3-CF₃—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 877 4-CF₃—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 878 3-i-PrO—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 879 3-i-Pr—C₆H₄ Me 1,2,4-Oxadiazol-3-yl 0 880 4-Cl-3-Me—C₆H₃ Me 1,2,4-Oxadiazol-3-yl 0 881 Pyridin-2-yl Me 1,2,4-Oxadiazol-3-yl 1 882 Pyridin-3-yl Me 1,2,4-Oxadiazol-3-yl 1 883 5-Cl- Me 1,2,4-Oxadiazol-3-yl 1 pyridin-2-yl 884 3-Cl- Me 1,2,4-Oxadiazol-3-yl 1 pyridin-2-yl 885 6-Cl- Me 1,2,4-Oxadiazol-3-yl 1 pyridin-2-yl 886 2-Cl- Me 1,2,4-Oxadiazol-3-yl 1 mp 177-178.5° C. pyridin-3-yl 887 5-CF₃- Me 1,2,4-Oxadiazol-3-yl 1 pyridin-2-yl 888 3-CF₃- Me 1,2,4-Oxadiazol-3-yl 1 pyridin-2-yl 889 6-CF₃-3-Cl- Me 1,2,4-Oxadiazol-3-yl 1 pyridin-2-yl 890 5-CF₃-3-Cl- Me 1,2,4-Oxadiazol-3-yl 1 pyridin-2-yl 891 Benzothiazol- Me 1,2,4-Oxadiazol-3-yl 1 2-yl 892 Benzoxazol- Me 1,2,4-Oxadiazol-3-yl 1 2-yl 893 Quinolin-2-yl Me 1,2,4-Oxadiazol-3-yl 1 894 5-CF₃-1,3,4- Me 1,2,4-Oxadiazol-3-yl 1 thiadiazol-2-yl 895 Pyrimidin-2-yl Me 1,2,4-Oxadiazol-3-yl 1 896 5-Cl-6-Me- Me 1,2,4-Qxadiazol-3-yl 1 pyrimidin-4-yl 897 5-Et-6-Me- Me 1,2,4-Oxadiazol-3-yl 1 pyrimidin-4-yl 898 6-Cl- Me 1,2,4-Oxadiazol-3-yl 1 pyrazin-2-yl 899 3,6-Me₂- Me 1,2,4-Oxadiazol-3-yl 1 pyrazin-2-yl 900 5-Me- Me 1,2,4-Oxadiazol-3-yl 1 isoxazol-3-yl 901 C₆H₅ Me 5-Me-1,2,4- 1 ¹H-NMR(CDCl₃) δ ppm: oxadiazol-3-yl 2.64(3H, s), 4.07(3H, s), 4.98(2H, s), 6.82-6.94(2H, m), 7.18-7.63(7H, m) 902 2-F—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 903 3-F—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 904 4-F—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 905 2-Cl—C₆H₄ Me 5-Me-1,2,4- 1 mp 88.5-89.5° C. oxadiazol-3-yl 906 3-Cl—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 907 4-Cl—C₆H₄ Me 5-Me-1,2,4- 1 mp 125-126° C. oxadiazol-3-yl 908 2-Br—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 909 3-Br—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 910 4-Br—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 911 3-I—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 912 2-Me—C₆H₄ Me 5-Me-1,2,4- 1 mp 86-87.5° C. oxadiazol-3-yl 913 3-Me—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 914 4-Me—C₆H₄ Me 5-Me-1,2,4- 1 mp 92.5-93.5° C. oxadiazol-3-yl 915 2-Et—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 916 3-Et—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 917 4-Et—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 918 2-MeO—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 919 3-MeO—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 920 4-MeO—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 921 2-CF₃—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 922 3-CF₃—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 923 4-CF₃—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 924 2,4-F₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 925 2,5-F₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 926 2,6-F₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 927 3,4-F₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 928 3,5-F₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 929 2,3-Cl₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 930 2,4-Cl₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 931 2,5-Cl₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 932 3,4-Cl₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 933 3,5-Cl₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 934 2,3-Me₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 935 2,4-Me₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 936 2,5-Me₂—C₆H₃ Me 5-Me-1,2,4- 1 Isomer A mp 98-100° C. oxadiazol-3-yl Isomer B mp 130-131.5° C. 937 3,4-Me₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 938 3,5-Me₂—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 939 2-Cl-4-Me—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 940 2-Cl-5-Me—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 941 4-Cl-2-Me—C₆H₃ Me 5-Me-1,2,4- 1 mp 115-116° C. oxadiazol-3-yl 942 4-Cl-3-Me—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 943 3-Ph—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 944 4-Ph—C₆H₄ Me 5-Me-1,2,4- 1 mp 124.5-125.5° C. oxadiazol-3-yl 945 3-i-PrO—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 946 3-i-Pr—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 947 4-i-Pr—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 948 3-t-Bu—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 949 2-MeS—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 950 4-MeS—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 951 2,3,6-F₃—C₆H₂ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 952 2,4,5-Cl₃—C₆H₂ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 953 3-PhO—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 954 3,4,5-(MeO)₃—C₆H₂ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 955 2,3,5-Me₃—C₆H₂ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 956 3,4,5-Me₃—C₆H₂ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 957 C₆F₅ Me 5-Me-1,2.4- 1 oxadiazol-3-yl 958 4-Cl-3-Et—C₆H₃ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 959 3-EtO—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 960 4-EtO—C₆H₄ Me 5-Me-1,2,4- 1 oxadiazol-3-yl 961 C₆H₅ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 962 4-F—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 963 3-Cl—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 964 4-Cl—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 965 3-Me—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 966 4-Me—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 967 4-Et—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 968 4-NO₂—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 969 3,4-Cl₂—C₆H₃ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 970 3,5-Cl₂—C₆H₃ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 971 3,4-Me—C₆H₃ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 972 3,5-Me—C₆H₃ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 973 3-PhO—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 974 4-Cl-3-Et—C₆H₃ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 975 3-EtO—C₆H₄ Me 5-Me-1,2.4- 0 oxadiazol-3-yl 976 3-CF₃—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 977 4-CF₃—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 978 3-i-PrO—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 979 3-i-Pr—C₆H₄ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 980 4-Cl-3-Me—C₆H₃ Me 5-Me-1,2,4- 0 oxadiazol-3-yl 981 Pyridin-2-yl Me 5-Me-1,2,4- 1 oxadiazol-3-yl 982 Pyridin-3-yl Me 5-Me-1,2,4- 1 oxadiazol-3-yl 983 5-Cl- Me 5-Me-1,2,4- 1 pyridin-2-yl oxadiazol-3-yl 984 3-Cl- Me 5-Me-1,2,4- 1 pyridin-2-yl oxadiazol-3-yl 985 6-Cl- Me 5-Me-1,2,4- 1 pyridin-2-yl oxadiazol-3-yl 986 2-Cl- Me 5-Me-1,2,4- 1 mp 82.5-84.5° C. pyridin-3-yl oxadiazol-3-yl 987 5-CF₃- Me 5-Me-1,2,4- 1 pyridin-2-yl oxadiazol-3-yl 988 3-CF₃- Me 5-Me-1,2,4- 1 pyridin-2-yl oxadiazol-3-yl 989 6-CF₃-3-Cl- Me 5-Me-1,2,4- 1 pyridin-2-yl oxadiazol-3-yl 990 5-CF₃-3-Cl- Me 5-Me-1,2,4- 1 pyridin-2-yl oxadiazol-3-yl 991 Benzothiazol- Me 5-Me-1,2,4- 1 2-yl oxadiazol-3-yl 992 Benzoxazol- Me 5-Me-1,2,4- 1 2-yl oxadiazol-3-yl 993 Quinolin-2-yl Me 5-Me-1,2,4- 1 oxadiazol-3-yl 994 5-CF₃-1,3,4- Me 5-Me-1,2,4- 1 thiadiazol-2-yl oxadiazol-3-yl 995 Pyrimidin-2-yl Me 5-Me-1,2,4- 1 oxadiazol-3-yl 996 5-Cl-6-Me- Me 5-Me-1,2,4- 1 pyrimidin-4-yl oxadiazol-3-yl 997 5-Et-6-Me- Me 5-Me-1,2,4- 1 pyrimidin-4-yl oxadiazol-3-yl 998 6-Cl- Me 5-Me-1,2,4- 1 pyrazin-2-yl oxadiazol-3-yl 999 3,6-Me₂- Me 5-Me-1,2,4- 1 pyrazin-2-yl oxadiazol-3-yl 1000 5-Me- Me 5-Me-1,2,4- 1 isoxazol-3-yl oxadiazol-3-yl 1001 C₆H₅ Me 1-Me-1H- 1 mp 83.0-84.5° C. tetrazol-5-yl 1002 2-F-C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yi 1003 3-F—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1004 4-F—C₆H₄ Me 1-Me-1H- 1 tetrazoi-5-yl 1005 2-Cl—C₆H₄ Me 1-Me-1H- 1 mp 118-119° C. tetrazol-5-yl 1006 3-Cl—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1007 4-Cl—C₆H₄ Me i-Me-1H- 1 mp 95-96° C. tetrazol-5-yl 1008 2-Br—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1009 3-Br—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1010 4-Br—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1011 3-I-C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1012 2-Me—C₆H₄ Me 1-Me-1H- 1 mp 111-112° C. tetrazol-5-yl 1013 3-Me—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1014 4-Me—C₆H₄ Me 1-Me-1H- 1 mp 138.5-139.5° C. tetrazol-5-yl 1015 2-Et—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1016 3-Et—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1017 4-Et—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1018 2-MeO—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1019 3-MeO—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1020 4-MeO—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1021 2-CF₃—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1 1022 3-CF₃—C₆H₄ Me 1-Me-1H- 1 ¹H-NMR(CDCl₃) δ ppm: tetrazol-5-yl 4.03(3H, s), 4.21(3H, s), 4.99(2H, s), 6.82-7.53(8H, m) 1023 4-CF₃—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1024 2,4-F₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1025 2,5-F₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1026 2,6-F₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1027 3,4-F₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1028 3,5-F₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1029 2,3-Cl₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1030 2,4-Cl₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1031 2,5-Cl₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1032 3,4-Cl₂—C₆H₃ Me 1-Me-1H- 1 mp 127-127.5° C. tetrazol-5-yl 1033 3,5-Cl₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1034 2,3-Me₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1035 2,4-Me₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1036 2,5-Me₂—C₆H₃ Me 1-Me-1H- 1 mp 115.5p14 116.5° C. tetrazol-5-yl 1037 3,4-Me₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1038 3,5-Me₂—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1039 2-Cl-4-Me—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1040 2-Cl-5-Me—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1041 4-Cl-2-Me—C₆H₃ Me 1-Me-1H- 1 mp 126.5-127.5° C. tetrazol-5-yl 1042 4-Cl-3-Me—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1043 3-Ph—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1044 4-Ph—C₆H₄ Me 1-Me-1H- 1 mp 130.5-131.5° C. tetrazol-5-yl 1045 3-i-PrO—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1046 3-i-Pr—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1047 4-i-Pr—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1048 3-t-Bu—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1049 2-MeS—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1050 4-MeS—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1051 2,3,6-F₃—C₆H₂ Me 1-Me-1H- 1 tetrazol-5-yl 1052 2,4,5-Cl₃—C₆H₂ Me 1-Me-1H- 1 tetrazol-5-yl 1053 3-PhO—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1054 3,4,5-(MeO)₃—C₆H₂ Me 1-Me-1H- 1 tetrazol-5-yl 1055 2,3,5-Me₃—C₆H₂ Me 1-Me-1H- 1 tetrazol-5-yl 1056 3,4,5-Me₃—C₆H₂ Me 1-Me-1H- 1 tetrazol-5-yl 1057 C₆F₅ Me 1-Me-1H- 1 tetrazol-5-yl 1058 4-Cl-3-Et—C₆H₃ Me 1-Me-1H- 1 tetrazol-5-yl 1059 3-EtO—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1060 4-EtO—C₆H₄ Me 1-Me-1H- 1 tetrazol-5-yl 1061 C₆H₅ Me 1-Me-1H- 0 tetrazol-5-yl 1062 4-F—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1063 3-Cl—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1064 4-Cl—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1065 3-Me—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1066 4-Me—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1067 4-Et—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1068 4-NO₂—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1069 3,4-Cl₂—C₆H₃ Me 1-Me-1H- 0 tetrazol-5-yl 1070 3,5-Cl₂—C₆H₃ Me 1-Me-1H- 0 tetrazol-5-yl 1071 3,4-Me₂—C₆H₃ Me 1-Me-1H- 0 tetrazol-5-yl 1072 3,5-Me₂—C₆H₃ Me 1-Me-1H- 0 tetrazol-5-yl 1073 3-PhO—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1074 4-Cl-3-Et—C₆H₃ Me 1-Me-1H- 0 tetrazol-5-yl 1075 3-EtO—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1076 3-CF₃—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1077 4-CF₃—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1078 3-i-PrO—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1079 3-i-Pr—C₆H₄ Me 1-Me-1H- 0 tetrazol-5-yl 1080 4-Cl-3-Me—C₆H₃ Me 1-Me-1H- 0 tetrazol-5-yl 1081 Pyridin-2-yl Me 1-Me-1H- 1 tetrazol-5-yl 1082 Pyridin-3-yl Me 1-Me-1H- 1 tetrazol-5-yl 1083 5-Cl- Me 1-Me-1H- 1 pyridin-2-yl tetrazol-5-yl 1084 3-Cl- Me 1-Me-1H- 1 pyridin-2-yl tetrazol-5-yl 1085 6-Cl- Me 1-Me-1H- 1 pyridin-2-yl tetrazol-5-yl 1086 2-Cl- Me 1-Me-1H- 1 pyridin-3-yl tetrazol-5-yl 1087 5-CF₃- Me 1-Me-1H- 1 pyridin-2-yl tetrazol-5-yl 1088 3-CF₃- Me 1-Me-1H- 1 pyridin-2-yl tetrazol-5-yl 1089 6-CF₃-3-Cl- Me 1-Me-1H- 1 pyridin-2-yl tetrazol-5-yl 1090 5-CF₃-3-Cl- Me 1-Me-1H- 1 pyridin-2-yl tetrazol-5-yl 1091 Benzothiazol- Me 1-Me-1H- 1 2-yl tetrazol-5-yl 1092 Benzoxazol- Me 1-Me-1H- 1 2-yl tetrazol-5-yl 1093 Quinolin-2-yl Me 1-Me-1H- 1 tetrazol-5-yl 1094 5-CF₃-1,3,4- Me 1-Me-1H- 1 thiadiazol-2-yl tetrazol-5-yl 1095 Pyrimidin-2-yl Me 1-Me-1H- 1 tetrazol-5-yl 1096 5-Cl-6-Me- Me 1-Me-1H- 1 pyrimidin-4-yl tetrazol-5-yl 1097 5-Et-6-Me- Me 1-Me-1H- 1 pyrimidin-4-yl tetrazol-5-yl 1098 6-Cl- Me 1-Me-1H- 1 pyrazin-2-yl tetrazol-5-yl 1099 3,6-Me₂- Me 1-Me-1H- 1 pyrazin-2-yl tetrazol-5-yl 1100 5-Me- Me 1-Me-1H- 1 isoxazol-3-yl tetrazol-5-yl 1101 C₆H₅ Me 1-Me-2- 1 ¹H-NMR(CDCl₃) δ ppm: 2.75(3H, s), imidazolin-2-yl 3.40(2H, t, J=9.8), 3.92(2H, t, J=9.8), 3.97(3H, s), 5.37(2H, s), 6.93-6.98(3H, m), 7.25-7.35(3H, m), 7.40(1H, t, J=7.5), 7.52(1H, d, J=7.5), 7.68(1H, d, J=7.5) 1102 2-F—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1103 3-F—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1104 4-F—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1105 2-CF₃—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1106 3-CF₃—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1107 4-CF₃—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1108 2-Br—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1109 3-Br—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1110 4-Br—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1111 3-I—6H₄ Me 1-Me-2- 1 imidazolin-2-yl 1112 2-Me—C₆H₄ Me 1-Me-2- 1 ¹H-NMR(CDCl₃) δ ppm: 2.33(3H, s), imidazolin-2-yl 2.74(3H, s), 3.40(2H, t, J=9.8), 3.93(2H, t, J=9.8), 4.02(3H, s), 5.38(2H, s), 6.82- 6.88(2H, m), 7.31-7.35(2H, m), 7.33(1H, t, J=7.7), 7.41(1H, t, J=7.7), 7.51(1H, d, J=7.7), 7.76(1H, d, J=7.7) 1113 3-Me—C₆H₄ Me 1-Me-2- 1 ¹H-NMR(CDCl₃) δ ppm: 2.32(3H, s), imidazolin-2-yl 2.75(3H, s), 3.40(2H, t, J=9.8), 3.92(2H, t, J=9.8), 3.90(3H, s), 5.35(2H, s), 6.75- 6.80(3H, m), 7.16(1H, t, J=7.6), 7.30- 7.43(2H, m), 7.51(1H, dd, J=7.6, 1.5), 7.68(1H, d, J=7.6) 1114 4-Me—C₆H₄ Me 1-Me-2- 1 ¹H-NMR(CDCl₃) δ ppm: 2.28(3H, s), imidazolin-2-yl 2.75(3H, s), 3.40(2H, t, J=9.8), 3.92(2H, t, J=9.8), 3.98(3H, s), 5.34(2H, s), 6.85(2H, d, J=8.5), 7.07(2H, d, J=8.5), 7.29-7.42(2H, m), 7.51(1H, dd, J=7.6, 1.5), 7.67(1H, d, J=7.6) 1115 2-Et—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1116 3-Et—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1117 4-Et—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1118 2-MeO—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1119 3-MeO—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1120 4-MeO—C₆H₄ Me 1-Me-2- 1 imidazolin-2-yl 1121 2-Cl—C₆H₄ Me 1-Me-2- 1 ¹H-NMR(CDCl₃) δ ppm: 2.75(3H, s), imidazolin-2-yl 3.41 (2H, t, J=9.8), 3.93(2H, t, J=9.8), 4.02(3H, s), 5.47(2H, s), 6.86-6.93(2H, m), 7.18(1H, ddd, J=8.5, 7.6, 1.5), 7.31- 7.45(3H, m), 7.49(1H, dd, J=7.6, 1.5), 7.81(1H, d, J=7.6) 1122 3-Cl—C₆H₄ Me 1-Me-2- 1 Isomer A ¹H-NMR(CDCl₃) δ ppm: 2.75(3H, imidazolin-2-yl s), 3.41 (2H, t, J=9.8), 3.92(2H, t, J=9.8), 3.97(3H, s), 5.35(2H, s), 6.84-6.99(3H, m), 7.19(1H, t, J=8.0), 7.32-7.44(2H, m), 7.51(1H, dd, J=7.3, 1.4), 7.64(1H, d, J=7.0) Isomer B ¹H-NMR(CDCl₃) δ ppm: 3.03(3H, s), 3.38(2H, t, J=9.9), 3.77(2H, t, J=9.9), 3.97(3H, s), 4.99(2H, s), 6.83-7.16(4H, m), 7.23(1H, d, J=7.6), 7.34-7.39(2H, m), 7.49(1H, d, J=6.4) 1123 4-Cl—C₆H₄ Me 1-Me-2- 1 mp 53-56° C. imidazolin-2-yl 1124 2,4-F₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1125 2,5-F₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1126 2,6-F₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1127 3,4-F₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1128 3,5-F₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1129 2,3-Cl₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1130 2,4-Cl₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1131 2,5-Cl₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1132 3,4-Cl₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1133 3,5-Cl₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1134 2,3-Me₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1135 2,4-Me₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1136 2,5-Me₂—C₆H₃ Me 1-Me-2- 1 mp 88-90° C. imidazolin-2-yl 1137 3,4-Me₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1138 3,5-Me₂—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1139 2-C1-4-Me—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1140 2-Cl-5-Me—C₆H₃ Me 1-Me-2- 1 imidazolin-2-yl 1141 4-Cl-2-Me—C₆H₃ Me 1-Me-2-imidazolin- 1 2-yl 1142 4-Cl-4-Me—C₆H₃ Me 1-Me-2-imidazolin 1 2-yl 1143 3-Ph—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1144 4-Ph—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1145 3-i-PrO—₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1146 3-i-Pr—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1147 4-i-Pr—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1148 3-t-Bu—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1149 2-MeS—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1150 4-MeS—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1151 2,3,6-F₃—C₆H₂ Me 1-Me-2-imidazolin- 1 2-yl 1152 2,4,5-Cl₃—C₆H₂ Me 1-Me-2-imidazolin- 1 2-yl 1153 3-PhO—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1154 3,4,5-(MeO)₃—C₆H₂ Me 1-Me-2-imidazolin- 1 2-yl 1155 2,3,5-Me₃—C₆H₂ Me 1-Me-2-imidazolin- 1 2-yl 1156 2,3,5-Me₃—C₆H₂ Me 1-Me-2-imidazolin- 1 2-yl 1157 C₆F₅ Me 1-Me-2-imidazolin- 1 2-yl 1158 4-Cl-3-Et—C₆H₃ Me 1-Me-2-imidazolin- 1 2-yl 1159 3-EtO—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1160 4-EtO—C₆H₄ Me 1-Me-2-imidazolin- 1 2-yl 1161 C₆H₅ Me 1-Me-2-imidazolin- 0 ¹H-NMR(CDCl₃) δ ppm: 2-yl 2.80(2.91 )(3H, s), 3.03(3.14)(2H, s), 3.53(3.61)(2H, t, J=9.8), 4.05(3.95)(3H, s), 6.96- 7.72(9H, m) 1162 4-F—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1163 3-Cl—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1164 4-Cl—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1165 3-Me—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1166 4-Me—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1167 4-Et—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1168 4-NO₂—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1169 3,4-Cl₂—C₆H₃ Me 1-Me-2-imidazolin- 0 2-yl 1170 3,5-Cl₂—C₆H₃ Me 1-Me-2-imidazolin- 0 2-yl 1171 3,4-Me₂—C₆H₃ Me 1-Me-2-imidazolin- 0 2-yl 1172 3,5-Me₂—C₆H₃ Me 1-Me-2-imidazolin- 0 2-yl 1173 3-PhO—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1174 4-Cl-3-Et—C₆H₃ Me 1-Me-2-imidazolin- 0 2-yl 1175 3-EtO—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1176 3-CF₃—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1177 4-CF₃—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1178 3-i-PrO—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1179 3-i-Pr—C₆H₄ Me 1-Me-2-imidazolin- 0 2-yl 1180 4-Cl-3-Me—C₆H₃ Me 1-Me-2-imidazolin- 0 2-yl 1181 Pyridin-2-yl Me 1-Me-2-imidazolin- 1 2-yl 1182 Pyridin-3-yl Me 1-Me-2-imidazolin 1 2-yl 1183 5-Cl- Me 1-Me-2-imidazolin- 1 pyridin-2-yl 2-yl 1184 3-Cl- Me 1-Me-2-imidazolin- 1 pyridin-2-yl 2-yl 1185 6-Cl- Me 1-Me-2-imidazolin- 1 pyridin-2-yl 2-yl 1186 2-Cl- Me 1-Me-2-imidazolin- 1 pyridin-3-yl 2-yl 1187 5-CF₃- Me 1-Me-2-imidazolin- 1 pyridin-2-yl 2-yl 1188 3-CF₃- Me 1-Me-2-imidazolin- 1 pyridin-2-yl 2-yl 1189 6-CF₃-3-Cl- Me 1-Me-2-imidazolin- 1 pyridin-2-yl 2-yl 1190 5-CF₃-3-Cl- Me 1-Me-2-imidazolin- 1 pyridin-2-yl 2-yl 1191 Benzothiazol- Me 1-Me-2-imidazolin- 1 -2-yl 2-yl 1192 Benzoxazol- Me 1-Me-2-imidazolin- 1 -2-yl 2-yl 1193 Quinolin-2-yl Me 1-Me-2-imidazolin- 1 2-yl 1194 5-CF₃-1,3,4- Me 1-Me-2-imidazolin- 1 thiadiazol-2-yl 2-yl 1195 Pyrimidin-2-yl Me 1-Me-2-imidazolin- 1 2-yl 1196 5-Cl-6-Me- Me 1-Me-2-imidazolin- 1 pyrimidin-4-yl 2-yl 1197 5-Et-6-Me- Me 1-Me-2-imidazolin- 1 pyrimidin-4-yl 2-yl 1198 6-Cl- Me 1-Me-2-imidazolin- 1 pyrazin-2-yl 2-yl 1199 3,6-Me₂- Me 1-Me-2-imidazolin- 1 pyrazin-2-yl 2-yl 1200 5-Me- Me 1-Me-2-imidazolin- 1 isoxazol-3-yl 2-yl 1201 C₆H₅ Me 2-Isoxazolin-3-yl 1 1202 2-F—C₆H₄ Me 2-Isoxazolin-3-yl 1 1203 3-F—C₆H₄ Me 2-Isoxazolin-3-yl 1 1204 4-F—C₆H₄ Me 2-Isoxazolin-3-yl 1 1205 2-Cl—C₆H₄ Me 2-Isoxazolin-3-yl 1 1206 3-Cl—C₆H₄ Me 2-Isoxazolin-3-yl 1 1207 4-Cl—C₆H₄ Me 2-Isoxazolin-3-yl 1 1208 2-Br—C₆H₄ Me 2-Isoxazolin-3-yl 1 1209 3-Br—C₆H₄ Me 2-Isoxazolin-3-yl 1 1210 4-Br—C₆H₄ Me 2-Isoxazolin-3-yl 1 1211 3-I—C₆H₄ Me 2-isoxazolin-3-yl 1 1212 2-Me—C₆H₄ Me 2-Isoxazolin-3-yl 1 1213 3-Me—C₆H₄ Me 2-Isoxazolin-3-yl 1 1214 4-Me—C₆H₄ Me 2-Isoxazolin-3-yl 1 1215 2-Et—C₆H₄ Me 2-Isoxazolin-3-yl 1 1216 3-Et—C₆H₄ Me 2-Isoxazolin-3-yl 1 1217 4-Et—C₆H₄ Me 2-Isoxazolin-3-yl 1 1218 2-MeO—C₆H₄ Me 2-Isoxazolin-3-yl 1 1219 3-MeO—C₆H₄ Me 2-Isoxazolin-3-yl 1 1220 4-MeO—C₆H₄ Me 2-Isoxazolin-3-yl 1 1221 2-CF₃—C₆H₄ Me 2-Isoxazolin-3-yl 1 1222 3-CF₃—C₆H₄ Me 2-Isoxazolin-3-yl 1 1223 4-CF₃—C₆H₄ Me 2-Isoxazolin-3-yl 1 1224 2,4-F₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1225 2,5-F₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1226 2,6-F₂—₆H₃ Me 2-Isoxazolin-3-yl 1 1227 3,4-F₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1228 3,5-F₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1229 2,3-Cl₂—C₆H₃ Me 2-Isaxazolin-3-yl 1 1230 2,4-Cl₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1231 2,5-Cl₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1232 3,4-Cl₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1233 3,5-Cl₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1234 2,3-Me₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1235 2,4-Me₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1236 2,5-Me₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 2.17-2.29(6H, m), 3.24- 3.38(2H, m), 3.95(4.00)(3H, s), 4.28(4.44)(2H, t, J=10.4), 4.93-5.06(2H, m), 6.59- 7.58(7H, m) 1237 3,4-Me₂—C₅H₃ Me 2-Isoxazolin-3-yl 1 1238 3,5-Me₂—C₆H₃ Me 2-Isoxazolin-3-yl 1 1239 2-Cl-4-Me—C₆H₃ Me 2-Isoxazolin-3-yl 1 1240 2-Cl-5-Me—C₆H₃ Me 2-Isoxazolin-3-yl 1 1241 4-Cl-2-Me—C₆H₃ Me 2-Isoxazolin-3-yl 1 1242 4-Cl-3-Me—C₆H₃ Me 2-Isoxazolin-3-yl 1 1243 3-Ph—C₆H₄ Me 2-Isoxazolin-3-yl 1 1244 4-Ph—C₆H₄ Me 2-Isoxazolin-3-yl 1 1245 3-i-PrO—C₆H₄ Me 2-Isoxazolin-3-yl 1 1246 3-i-Pr—C₆H₄ Me 2-Isaxazolin-3-yl 1 1247 4-i-Pr—C₆H₄ Me 2-Isoxazolin-3-yl 1 1248 3-t-Bu—C₆H₄ Me 2-Isoxazolin-3-yl 1 1249 2-MeS—C₆H₄ Me 2-Isoxazolin-3-yl 1 1250 4-MeS—C₆H₄ Me 2-Isoxazolin-3-yl 1 1251 2,3,6-F₃—C₆H₂ Me 2-Isoxazolin-3-yl 1 1252 2,4,5-Cl₃—C₆H₂ Me 2-Isoxazolin-3-yl 1 1253 3-PhO—C₆H₄ Me 2-Isoxazolin-3-yl 1 1254 3,4,5-(MeO)₃—C₆H₂ Me 2-Isoxazolin-3-yl 1 1255 2,3,5-Me₃—C₆H₂ Me 2-Isoxazolin-3-yl 1 1256 3,4,5-Me₃—C₆H₂ Me 2-Isoxazolin-3-yl 1 1257 C₆F₅ Me 2-Isoxazolin-3-yl 1 1258 4-Cl-3-Et—C₆H₃ Me 2-Isoxazolin-3-yl 1 1259 3-EtO-C₆H₄ Me 2-Isoxazolin-3-yl 1 1260 4-EtO—C₆H₄ Me 2-Isoxazolin-3-yl 1 1261 C₆H₅ Me 2-Isoxazolin-3-yl 0 1262 4-F—C₆H₄ Me 2-Isoxazolin-3-yl 0 1263 3-Cl—C₆H₄ Me 2-Isoxazolin-3-yl 0 1264 4-Cl—C₆H₄ Me 2-Isoxazolin-3-yl 0 1265 3-Me—C₆H₄ Me 2-Isoxazolin-3-yl 0 1266 4-Me—C₆H₄ Me 2-Isoxazolin-3-yl 0 1267 4-Et—C₆H₄ Me 2-Isoxazolin-3-yl 0 1268 4-NO₂p13 C₆H₄ Me 2-Isoxazolin-3-yl 0 1269 3,4-Cl₂—C₆H₃ Me 2-Isoxazolin-3-yl 0 1270 3,5-Cl₂—C₆H₃ Me 2-Isoxazolln-3-yl 0 1271 3,4-Me₂—C₆H₃ Me 2-Isoxazolin-3-yl 0 1272 3,5-Me₂p13 C₆H₃ Me 2-Isoxazolin-3-yl 0 1273 3-PhO—C₆H₄ Me 2-Isoxazolin-3-yl 0 1274 4-Cl-3-Et—C₆H₃ Me 2-Isoxazolin-3-yl 0 1275 3-EtO—C₆H₄ Me 2-Isoxazolin-3-yl 0 1276 3-CF₃—C₆H₄ Me 2-Isoxazolin-3-yl 0 1277 4-CF₃—C₆H₄ Me 2-Isoxazolin-3-yl 0 1278 3-i-PrO—C₆H₄ Me 2-Isoxazolin-3-yl 0 1279 3-i-Pr—C₆H₄ Me 2-Isoxazolin-3-yl 0 1280 4-Cl-3-Me—C₆H₃ Me 2-Isoxazolin-3-yl 0 1281 Pyridin-2-yl Me 2-Isoxazolin-3-yl 1 1282 Pyridin-3-yl Me 2-Isoxazolin-3-yl 1 1283 5-Cl- Me 2-Isoxazolin-3-yl 1 pyridin-2-yl 1284 3-Cl- Me 2-Isoxazolin-3-yl 1 pyridin-2-yl 1285 6-Cl- Me 2-Isoxazolin-3-yl 1 pyridin-2-yl 1286 2-Cl- Me 2-Isoxazolin-3-yl 1 pyridin-3-yl 1287 5-CF₃- Me 2-Isoxazolin-3-yl 1 pyridin-2-yl 1288 3-CF₃- Me 2-Isoxazolin-3-yl 1 pyridin-2-yl 1289 6-CF₃-3-Cl- Me 2-Isoxazolin-3-yl 1 pyridin-2-yl 1290 5-CF₃-3-Cl- Me 2-Isoxazolin-3-yl 1 pyridin-2-yl 1291 Benzothiazol- Me 2-Isoxazolin-3-yl 1 2-yl 1292 Benzoxazol- Me 2-Isoxazolin-3-yl 1 2-yl 1293 Quinolin-2-yl Me 2-Isoxazolin-3-yl 1 1294 5-CF₃-1,3,4- Me 2-Isoxazolin-3-yl 1 thiadiazol-2-yl 1295 Pyrimidin-2-yl Me 2-Isoxazolin-3-yl 1 1296 5-Cl-6-Me- Me 2-Isoxazolin-3-yl 1 pyrimidin-4-yl 1297 5-Et-6-Me- Me 2-Isoxazolin-3-yl 1 pyrimidin-4-yl 1298 6-Cl- Me 2-Isoxazolin-3-yl 1 pyrazin-2-yl 1299 3,6-Me₂- Me 2-Isoxazolin-3-yl pyrazin-2-yl 1300 5-Me- Me 2-Isoxazolin-3-yl 1 isoxazol-3-yl 1301 C₆H₅ Me 2-Oxazolin-2-yl 1 mp 69-70° C. 1302 2-F—C₆H₄ Me 2-Oxazolin-2-yl 1 1303 3-F—C₆H₄ Me 2-Oxazolin-2-yl 1 1304 4-F—C₆H₄ Me 2-Oxazolin-2-yl 1 1305 2-Cl—C₆H₄ Me 2-Oxazolin-2-yl 1 mp 89-90° C. 1306 3-Cl—C₆H₄ Me 2-Oxazolin-2-yl 1 mp 82-83° C. 1307 4-Cl‘C₆H₄ Me 2-Oxazolin-2-yl 1 mp 76-80° C. 1308 3-Br—C₆H₄ Me 2-Oxazolin-2-yl 1 1309 4-Br—C₆H₄ Me 2-Oxazolin-2-yl 1 1310 2-Me—C₆H₄ Me 2-Oxazolin-2-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.30(3H, s), 4.02(2H, t, J=9.8), 4.05(3H, s), 4.32(2H, t, J=9.8), 5.25(2H, s), 6.82(1H, d, J=8.3), 6.86(1 H, t, J=7.6), 7.10-7.16(2H, m), 7.35(1H, t, J=7.6), 7.41-7.48(2H, m), 7.68(1H, d, J=7.6) 1311 3-Me—C₆H₄ Me 2-Oxazolin-2-yl 1 ¹H-NMR(CDC₃) δ ppm: 2.31(3H, s), 4.00(2H, t, J=9.8), 4.03(3H, s), 4.32(2H, t, J=9.8), 5.21(2H, s), 6.72-6.78(3H, m), 7.14(1H, t, J=7.6), 7.31- 7.48(3H, m), 7.62(1H, d, J=7.6) 1312 4-Me—C₆H₄ Me 2-Oxazolin-2-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.27(3H, s), 4.00(2H, t, J=9.6). 4.03(3H, s), 4.31(2H, t, J=9.6), 5.20(2H, s), 6.84(2H, d, J=8.6), 7.06(21-i, d, J=8.6), 7.31-7.47(3H, m), 7.62(1 H, d, J=7.6) 1313 3-Et—C₆H₄ Me 2-Oxazolin-2-yl 1 1314 2-MeO—C₆H₄ Me 2-Oxazolin-2-yl 1 1315 3-MeO—C₆H₄ Me 2-Oxazolin-2-yl 1 1316 4-MeO—C₆H₄ Me 2-Oxazolin-2-yl 1 1317 4-Et—C₆H₄ Me 2-Oxazolin-2-yl 1 1318 3-CF₃—C₆H₄ Me 2-Oxazolin-2-yl 1 1319 4-CF₃—C₆H₄ Me 2-Oxazolin-2-yl 1 1320 3,5-F₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1321 2,3-Cl₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1322 2,4-Cl₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1323 2,5-Cl₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1324 3,4-Cl₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1325 3,5-Cl₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1326 2,3-Me₂—C₅H₃ Me 2-Oxazolin-2-yl 1 1327 2,4-Me₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1328 2,5-Me₂—C₆H₃ Me 2-Oxazolin-2-yl 1 mp 81-85° C. 1329 3,4-Me₂—C₆H₃ Me 2-Oxazolin-2-yl 1 1330 2-Cl-4-Me—C₆H₃ Me 2-Oxazolin-2-yl 1 1331 2-Cl-5-Me—C₆H₃ Me 2-Oxazolin-2-yl 1 1332 4-Cl-3-Me—C₆H₃ Me 2-Oxazolin-2-yl 1 1333 3-Ph—C₆H₄ Me 2-Oxazolin-2-yl 1 1334 3-i-PrO—C₆H₄ Me 2-Oxazolin-2-yl 1 1335 3-PhO—C₆H₄ Me 2-Oxazolin-2-yl 1 1336 4-Cl-2-Me—C₆H₃ Me 2-Oxazolin-2-yl 1 1337 4-Cl-3-Et—C₆H₃ Me 2-Oxazolin-2-yl 1 1338 3-EtO—C₆H₄ Me 2-Oxazolin-2-yl 1 1339 2-Cl-4-Me—C₆H₃ Me 2-Oxazolin-2-yl 1 1340 2,4,5-Cl₃—C₆H₂ Me 2-Oxazolin-2-yl 1 1341 C₆H₅ Me 2-Oxazolin-2-yl 0 Isomer A: ¹H-NMR(CDCl₃) δ ppm: 3.63(2H, t, J=9.8), 4.08(308(2H, t, J=9.8), 6.94- 7.40(8H, m), 7.69(1 H, dd, J=7.9, 1.9) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 3.91 (2H, t, J=9.8), 3.96(3H, s), 4.37(2H, t, J=9.8), 6.91-7.37(9H, m) 1342 4-F—C₆H₄ Me 2-Oxazolin-2-yl 0 1343 3-Cl—C₆H₄ Me 2-Oxazolin-2-yl 0 1344 4-Cl—C₆H₄ Me 2-Oxazolin-2-yl 0 1345 4-Me—C₆H₄ Me 2-Oxazolin-2-yl 0 1346 3,5-Cl₂—C₆H₃ Me 2-Oxazolin-2-yl 0 1347 3,4-Me₂—C₆H₃ Me 2-Oxazolin-2-yl 0 1318 2-Cl- Me 2-Oxazolin-2-yl 1 pyridin-3-yl 1349 5-CF₃- Me 2-Oxazolin-2-yl 1 pyridin-2-yl 1350 5-Cl- Me 2-Oxazolin-2-yl 1 pyridin-2-yl 1351 C₆H₅ Me 5-Me-2-isoxazolin- 1 3-yl 1352 2-F—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1353 3-F—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1354 4-F—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1355 2-Cl—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1356 3-Cl—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1357 4-Cl—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1358 3-Br—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1359 4-Br—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1360 2-Me—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1361 3-Me—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1362 4-Me—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1363 3-Et—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1364 2-MeO—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1365 3-MeO—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1366 4-MeO—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1367 4-Et—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1368 3-CF₃—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1369 4-CF₃—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1370 3,5-F₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1371 2,3-Cl2—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1372 2,4-Cl₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1373 2,5-Cl₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1374 3,4-Cl₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1375 3,5-Cl₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1376 2,3-Me₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1377 2,4-Me₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1378 2,5-Me₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1379 3,4-Me₂—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1380 2-C1-4-Me—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1381 2-Cl-5-Me—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1382 4-Cl-3-Me—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1383 3-Ph—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1384 3-i-PrO—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1385 3-PhO—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1386 4-Cl-2-Me—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1387 4-Cl-3-Et—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1388 3-EtO—C₆H₄ Me 5-Me-2-isoxazolin- 1 3-yl 1389 2-Cl-4-Me—C₆H₃ Me 5-Me-2-isoxazolin- 1 3-yl 1390 2,4,5-Cl₃—C₆H₂ Me 5-Me-2-isoxazolin- 1 3-yl 1391 C₆H₅ Me 5-Me-2-isoxazolin- 0 3-yl 1392 4-F—C₆H₄ Me 5-Me-2-isoxazolin- 0 3-yl 1393 3-Cl—C₆H₄ Me 5-Me-2-isoxazolin- 0 3-yl 1394 4-Cl—C₆H₄ Me 5-Me-2-isoxazolin- 0 3-yl 1395 4-Me—C₆H₄ Me 5-Me-2-isoxazolin- 0 3-yl 1396 3,5-Cl₂—C₆H₃ Me 5-Me-2-isoxazolin- 0 3-yl 1397 3,4-Me₂—C₆H₃ Me 5-Me-2-isoxazolin- 0 3-yl 1398 2-Cl- Me 5-Me-2-isoxazolin- 1 pyridin-3-yl 3-yl 1399 5-CF₃- Me 5-Me-2-isoxazolin- 1 pyridin-2-yl 3-yl 1400 5-Cl- Me 5-Me-2-isoxazolin- 1 pyridin-2-yl 3-yl 1401 C₆H₅ Me imidazol-2-yl 1 1402 2-F—C₆H₄ Me Imidazol-2-yl 1 1403 3-F—C₆H₄ Me Imidazol-2-yl 1 1404 4-F—C₆H₄ Me Imidazol-2-yl 1 1405 2-Cl—C₆H₄ Me Imidazol-2-yl 1 1406 3-Cl—C₆H₄ Me Imidazol-2-yl 1 1407 4-Cl—C₆H₄ Me Imidazol-2-yl 1 1408 3-Br—C₆H₄ Me Imidazol-2-yl 1 1409 4-Br—C₆H₄ Me Imidazol-2-yl 1 1410 2-Me—C₆H₄ Me Imidazol-2-yl 1 1411 3-Me—C₆H₄ Me Imidazol-2-yl 1 1412 4-Me—C₆H₄ Me Imidazol-2-yl 1 1413 3-Et—C₆H₄ Me Imidazol-2-yl 1 1414 2-MeO—C₆H₄ Me Imidazol-2-yl 1 1415 3-MeO—C₆H₄ Me Imidazol-2-yl 1 1416 4-MeO—C₆H₄ Me Imidazol-2-yl 1 1417 4-Et—C₆H₄ Me Imidazol-2-yl 1 1418 3-CF₃—C₆H₄ Me Imidazol-2-yl 1 1419 4-CF₃—C₆H₄ Me Imidazol-2-yl 1 1420 3,5-F₂—C₆H₃ Me Imidazol-2-yl 1 1421 2,3-Cl₂—C₆H₃ Me Imidazol-2-yl 1 1422 2,4-Cl₂—C₆H₃ Me Imidazol-2-yl 1 1423 2,5-Cl₂—C₆H₃ Me Imidazol-2-yl 1 1424 3,4-Cl₂—C₆H₃ Me Imidazol-2-yl 1 1425 3,5-Cl₂—C₆H₃ Me Imidazol-2-yl 1 1426 2,3-Me₂—C₆H₃ Me Imidazol-2-yl 1 1427 2,4-Me₂—C₆H₃ Me Imidazol-2-yl 1 1428 2,5-Me₂—C₆H₃ Me Imidazol-2-yl 1 mp 153-154° C. 1429 3,4-Me₂—C₆H₃ Me Imidazol-2-yl 1 1430 2-Cl-4-Me—C₆H₃ Me Imidazol-2-yl 1 1431 2-Cl-5-Me—C₆H₃ Me Imidazol-2-yl 1 1432 4-Cl-3-Me—C₆H₃ Me Imidazol-2-yl 1 1433 3-Ph—C₆H₄ Me Imidazol-2-yl 1 1434 3-i-PrO—C₆H₄ Me Imidazol-2-yl 1 1435 3-PhO—C₆H₄ Me Imidazol-2-yl 1 1436 4-Cl-2-Me—C₆H₃ Me Imidazol-2-yl 1 1437 4-Cl-3-Et—C₆H₃ Me Imidazol-2-yl 1 1438 3-EtO—C₆H₄ Me Imidazol-2-yl 1 1439 2-Cl-4-Me—C₆H₃ Me Imidazol-2-yl 1 1440 2,4,5-Cl₃—C₆H₂ Me Imidazol-2-yl 1 1441 C₆H₅ Me Imidazol-2-yl 0 1442 4-F—C₆H₄ Me Imidazol-2-yl 0 1443 3-Cl—C₆H₄ Me Imidazol-2-yl 0 1444 4-Cl—C₆H₄ Me Imidazol-2-yl 0 1445 4-Me—C₆H₄ Me Imidazol-2-yl 0 1446 3,5-Cl₂—C₆H₃ Me Imidazol-2-yl 0 1447 3,4-Me₂—C₆H₃ Me Imidazol-2-yl 0 1448 2-Cl- Me Imidazol-2-yl 1 pyridin-3-yl 1449 5-CF₃- Me Imidazol-2-yl 1 pyridin-2-yl 1450 5-Cl- Me Imidazol-2-yl 1 pyridin-2-yl 1451 C₆H₅ Me 2-Imidazolin-2-yl 1 mp 91-92° C. 1452 2-F—C₆H₄ Me 2-Imidazolin-2-yl 1 1453 3-F—C₆H₄ Me 2-Imidazolin-2-yl 1 1454 4-F—C₆H₄ Me 2-Imidazolin-2-yl 1 1455 2-Cl—C₆H₄ Me 2-Imidazolin-2-yl 1 mp 121-123° C. 1456 3-Cl—C₆H₄ Me 2-Imidazolin-2-yl 1 ¹H-NMR(CDCl₃) δ ppm: 3.67(4H, brs), 3.95(4.02)(3H, s), 4.97(5.11)(2H, s), 6.78- 6.81(1H, m), 6.90-6.95(2H, m), 7.13-7.23(2H, m), 7.35- 7.41(2H, m), 7.49-7.51(1H, m) 1457 4-Cl—C₆H₄ Me 2-Imidazolin-2-yl 1 mp 113-114° C. 1458 3-Br—C₆H₄ Me 2-Imidazolin-2-yl 1 1459 4-Br—C₆H₄ Me 2-Imidazolin-2-yl 1 1460 2-Me—C₆H₄ Me 2-Imidazolin-2-yl 1 mp 96-100° C. 1461 3-Me—C₆H₄ Me 2-Imidazolin-2-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.31(2.27)(3H, s), 3.66(4H, brs), 4.02(3.94)(3H, s), 5.11(4.95)(2H, s), 6.54- 6.76(3H, m), 7.04-7.15(1H, m), 7.21-7.41(3H, m), 7.50- 7.53(1H, m) 1462 4-Me—C₆H₄ Me 2-Imidazolin-2-yl 1 mp 89-90° C. 1463 3-Et—C₆H₄ Me 2-Imidazolin-2-yl 1 1464 2-MeO—C₆H₄ Me 2-Imidazolin-2-yl 1 1465 3-MeO—C₆H₄ Me 2-Imidazolin-2-yl 1 1466 4-MeO—C₆H₄ Me 2-Imidazolin-2-yl 1 1467 4-Et—C₆H₄ Me 2-Imidazolin-2-yl 1 1468 3-CF₃—C₆H₄ Me 2-Imidazolin-2-yl 1 1469 4-CF₃—C₆H₄ Me 2-Imidazolin-2-yl 1 1470 3,5-F₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1471 2,3-Cl₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1472 2,4-Cl₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1473 2,5-Cl₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1474 3,4-Cl₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1475 3,5-Cl₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1476 2,3-Me₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1477 2,4-Me₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1478 2,5-Me₂—C₆H₃ Me 2-Imidazolin-2-yl 1 mp 97-101° C. 1479 3,4-Me₂—C₆H₃ Me 2-Imidazolin-2-yl 1 1480 2-Cl-4-Me—C₆H₃ Me 2-Imidazolin-2-yl 1 1481 2-Cl-5-Me—C₆H₃ Me 2-Imidazolin-2-yl 1 1482 4-Cl-3-Me—C₆H₃ Me 2-Imidazolin-2-yl 1 1483 3-Ph—C₆H₄ Me 2-Imidazolin-2-yl 1 1484 3-i-PrO—C₆H₄ Me 2-Imidazolin-2-yl 1 1485 3-PhO—C₆H₄ Me 2-Imidazolin-2-yl 1 1486 4-Cl-2-Me—C₆H₃ Me 2-Imidazolin-2-yl 1 1487 4-Cl-3-Et—C₆H₃ Me 2-Imidazolin-2-yl 1 1488 3-EtO—C₆H₄ Me 2-Imidazolin-2-yl 1 1489 2-Cl-4-Me—C₆H₃ Me 2-Imidazolin-2-yl 1 1490 2,4,5-Cl₃—C₆H₂ Me 2-Imidazolin-2-yl 1 1491 C₆H₅ Me 2-Imidazolin-2-yl 0 mp 95-99° C. 1492 4-F—C₆H₄ Me 2-Imidazolin-2-yl 0 1493 3-Cl—C₆H₄ Me 2-Imidazolin-2-yl 0 1494 4-Cl—C₆H₄ Me 2-Imidazolin-2-yl 0 1495 4-Me—C₆H₄ Me 2-Imidazolin-2-yl 0 1496 3,5-Cl₂—C₆H₃ Me 2-Imidazolin-2-yl 0 1497 3,4-Me₂—C₆H₃ Me 2-Imidazolin2-yl 0 1498 2-Cl- Me 2-Imidazolin-2-yl 1 pyridin-3-yl 1499 5-CF₃- Me 2-Imidazolin-2-yl 1 pyridin-2-yl 1500 5-Cl- Me 2-Imidazolin-2-yl 1 pyridin-2-yl 1501 C₆H₅ Me 2-Thiazolin-2-yl 1 1502 2-Cl—C₆H₄ Me 2-Thiazolin-2-yl 1 1503 3-Cl—C₆H₄ Me 2-Thiazolin-2-yl 1 1504 4-Cl—C₆H₄ Me 2-Thiazolin-2-yl 1 1505 2-Me—C₆H₄ Me 2-Thiazolin-2-yl 1 1506 3-Me—C₆H₄ Me 2-Thiazolin-2-yl 1 1507 4-Me—C₆H₄ Me 2-Thiazolin-2-yl 1 1508 2-MeO—C₆H₄ Me 2-Thiazolin-2-yl 1 1509 4-Br—C₆H₄ Me 2-Thiazolin-2-yl 1 1510 3-CF₃—C₆H₄ Me 2-Thiazolin-2-yl 1 1511 2,4-Cl₂—C₆H₃ Me 2-Thiazolin-2-yl 1 1512 2,5-Cl₂—C₆H₃ Me 2-Thiazolin-2-yl 1 1513 2,4-Me₂—C₆H₃ Me 2-Thiazolin-2-yl 1 1514 2,5-Me₂—C₆H₃ Me 2-Thiazolin-2-yl 1 mp 79-82° C. 1515 C₆H₅ Me 2-Thiazolin-2-yl 0 ¹H-NMR(CDCl₃) δ ppm: 2.88(3.22)(2H, t, J=8.0), 3.90(4.29)(2H, t, J=8.0), 4.06(3.95)(3H, s), 6.91- 7.58(9H, m) 1516 4-Cl—C₆H₄ Me 2-Thiazolin-2-yl 0 1517 4-Me—C₆H₄ Me 2-Thiazolin-2-yl 0 1518 2-Cl- Me 2-Thiazolin-2-yl 1 pyridin-3-yl 1519 5-CF₃- Me 2-Thiazolin-2-yl 1 pyridin-2-yl 1520 5-Cl- Me 2-Thiazolin-2-yl 1 pyridin-2-yl 1521 C₆H₅ Me Thiazol-2-yl 1 1522 2-Cl—C₆H₄ Me Thiazol-2-yl 1 1523 3-Cl—C₆H₄ Me Thiazol-2-yl 1 1524 4-Cl—C₆H₄ Me Thiazol-2-yl 1 1525 2-Me—C₆H₄ Me Thiazol-2-yl 1 1526 3-Me—C₆H₄ Me Thiazol-2-yl 1 1527 4-Me—C₆H₄ Me Thiazol-2-yl 1 1528 2-MeO—C₆H₄ Me Thiazol-2-yl 1 1529 4-Br—C₆H₄ Me Thiazol-2-yl 1 1530 3-CF₃—C₆H₄ Me Thiazol-2-yl 1 1532 2,5-Cl₂—C₆H₃ Me Thiazol-2-yl 1 1533 2,4-Me₂—C₆H₃ Me Thiazol-2-yl 1 1534 2,5-Me₂—C₆H₃ Me Thiazol-2-yl 1 mp 112-113.5° C. 1535 C₆H₅ Me Thiazol-2-yl 0 1536 4-Cl—C₆H₄ Me Thiazol-2-yl 0 1537 4-Me—C₆H₄ Me Thiazol-2-yl 0 1538 2-Cl- Me Thiazol-2-yl 1 pyridin-3-yl 1539 5-CF₃- Me Thiazol-2-yl 1 pyridin-2-yl 1540 5-Cl- Me Thiazol-2-yl 1 pyridin-2-yl 1541 C₆H₅ Me 1-Me-pyrazol-5-yl 1 1542 2-Cl—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1543 3-Cl—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1544 4-Cl—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1545 2-Me—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1546 3-Me—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1547 4-Me—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1548 2-MeO—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1549 4-Br—C₆H₄ Me 1-Me-pyrazol-5-yl 1 1550 2,5-Me₂—C₆H₃ Et 1-Me-pyrazol-5-yl 1 Isomer A: mp 74-76° C. Isomer B: mp 84-86° C. 1551 2,4-Cl₂—C₆H₃ Me 1-Me-pyrazol-5-yl 1 1552 2,5-Cl₂—C₆H₃ Me 1-Me-pyrazol-5-yl 1 1553 2,4-Me₂—C₆H₃ Me 1-Me-pyrazol-5-yl 1 1554 2,5-Me₂—C₆H₃ Me 1-Me-pyrazol-5-yl 1 Isomer A: ¹H-NMR(CDCl₃) δ ppm: 2.12(3H, s), 2.24(3H, s), 3.98(3H, s), 4.12(3H, s), 4.93(2H, s), 5.92(1H, d, J=1.8), 6.52(1H, s), 6.64- 7.64(7H, m) Isomer B: mp 108-110° C. 1555 C₆H₅ Me 1-Me-pyrazol-5-yl 0 1556 4-Cl—C₆H₄ Me 1-Me-pyrazol-5-yl 0 1557 4-Me—C₆H₄ Me 1-Me-pyrazol-5-yl 0 1558 2-Cl- Me 1-Me-pyrazol-5-yl 1 pyridin-3-yl 1559 5-CF₃- Me 1-Me-pyrazol-6-yl 1 pyridin-2-yl 1560 5-Cl- Me 1-Me-pyrazol-5-yl 1 pyridin-2-yl 1561 C₆H₅ Me 1-Me-1,2,4-triazol- 1 ¹H-NMR(CDCl₃) δ ppm: 5-yl 4.00(3H, s), 4.03(3H, s), 4.92(2H, s), 6.74-6.94(3H, m), 7.18-7.57(5H, m), 7.83(1H, s) 1562 2-Cl—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1563 3-Cl—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1564 4-Cl—C₆H₄ Me 1-Me-1,2,4-triazol- 1 mp 113-114°]C. 5-yl 1565 2-Me—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1566 3-Me—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1567 4-Me—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1568 2-MeO—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1569 4-Br—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1570 3-CF₃—C₆H₄ Me 1-Me-1,2,4-triazol- 1 5-yl 1571 2,4-Cl₂—C₆H₃ Me 1-Me-1,2,4-triazol- 1 5-yl 1572 2,5-Cl₂—C₆H₃ Me 1-Me-1,2,4-triazol- 1 5yl 1573 2,4-Me₂—C₆H₃ Me 1-Me-1,2,4-triazol- 1 5-yl 1574 2,5-Me₂—C₆H₃ Me 1-Me-1,2,4-triazol- 1 mp 101-102° C. 5-yl 1575 C₆H₅ Me 1-Me-1,2,4-triazol- 1 3.98(6H, s), 6.85-7.48(9H, m), 5-yl 7.80(1H, s) 1576 4-Cl—C₆H₄ Me 1-Me-1,2,4-triazol- 0 5-yl 1577 4-Me—C₆H₄ Me 1-Me-1,2,4-triazol- 0 5-yl 1578 2-Cl- Me 1-Me-1,2,4-triazol- 1 mp 99-100° C. pyridin-3-yl 5-yl 1579 5-CF₃- Me 1-Me-1,2,4-triazol- 1 pyridin-2-yl 5-yl 1580 5-Cl- Me 1-Me-1,2,4-triazol- 1 pyridin-2-yl 5-yl 1581 C₆H₅ Me 1,2,4-Oxadiazol-5-yl 1 mp 109.0-110.0° C. 1582 2-Cl—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 1583 3-Cl—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 1584 4-Cl—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 mp 96-97.5° C. 1585 2-Me—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 1586 3-Me—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 1587 4-Me—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 1588 2-MeO—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 1589 4-Br—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 1 1590 2,5-Me₂—C₆H₃ Me 3-Et-1,2,4- 1 mp 111.5-112.5° C. oxadiazol-5-yl 1591 2,4-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-5-yl 1 1592 2,5-Cl₂—C₆H₃ Me 1,2,4-Oxadiazol-5-yl 1 1593 2,4-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-5-yl 1 1594 2,5-Me₂—C₆H₃ Me 1,2,4-Oxadiazol-5-yl 1 mp 75-76° C. 1595 C₆H₅ Me 1,2,4-Oxadiazol-5-yl 0 mp 115.5-116.5° C. 1596 4-Cl—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 0 1597 4-Me—C₆H₄ Me 1,2,4-Oxadiazol-5-yl 0 1598 2-Cl- Me 1,2,4-Oxadiazol-5-yl 1 pyridin-3-yl 1599 5-CF₃- Me 1,2,4-Oxadiazol-5-yl 1 pyridin-2-yl 1600 5-Cl- Me 1,2,4-Oxadiazol-5-yl 1 pyridin-2-yl 1601 C₆H₅ Me 2-Thienyl 1 1602 2-Cl-C₆H₄ Me 2-Thienyl 1 1603 3-Cl—C₆H₄ Me 2-Thienyl 1 1604 4-Cl—C₆H₄ Me 2-Thienyl 1 1605 2-Me—C₆H₄ Me 2-Thienyl 1 1606 3-Me—C₆H₄ Me 2-Thienyl 1 1607 4-Me—C₆H₄ Me 2-Thienyl 1 1608 2-MeO—C₆H₄ Me 2-Thienyl 1 1609 4-Br—C₆H₄ Me 2-Thienyl 1 1610 3-CF₃—C₆H₄ Me 2-Thienyl 1 1611 2,4-Cl₂—C₆H₃ Me 2-Thienyl 1 1612 2,5-Cl₂—C₆H₃ Me 2-Thienyl 1 1613 2,4-Me₂—C₆H₃ Me 2-Thienyl 1 1614 2,5-Me₂—C₆H₃ Me 2-Thienyl 1 Isomer A: mp 81-84° C. Isomer B: mp 106-107° C. 1615 C₆H₅ Me 2-Thienyl 0 1616 4-Cl—C₆H₄ Me 2-Thienyl 0 1617 4-Me—C₆H₄ Me 2-Thienyl 0 1618 2-Cl- Me 2-Thienyl 1 pyridin-3-yl 1619 5-CF₃- Me 2-Thienyl 1 pyridin-2-yl 1620 5-Cl- Me 2-Thienyl 1 pyridin-2-yl 1621 C₆H₅ Me 2-Furyl 1 1622 2-Cl—C₆H₄ Me 2-Furyl 1 1623 3-Cl—C₆H₄ Me 2-Furyl 1 1624 4-Cl—C₆H₄ Me 2-Furyl 1 1625 2-Me—C₆H₄ Me 2-Furyl 1 1626 3-Me—C₆H₄ Me 2-Furyl 1 1627 4-Me—C₆H₄ Me 2-Furyl 1 1628 2-MeO—C₆H₄ Me 2-Furyl 1 1629 4-Br—C₆H₄ Me 2-Furyl 1 1630 3-CF₃—C₆H₄ Me 2-Furyl 1 1631 2,4-Cl₂—C₆H₃ Me 2-Furyl 1 1632 2,5-Cl₂—C₆H₃ Me 2-Furyl 1 1633 2,4-Me₂—C₆H₃ Me 2-Furyl 1 1634 2,5-Me₂—C₆H₃ Me 2-Furyl 1 Isomer A: mp 81-82° C. Isomer B: mp 110-112° C. 1635 C₆H₅ Me 2-Furyl 0 1636 4-Cl—C₆H₄ Me 2-Furyl 0 1637 4-Me—C₆H₄ Me 2-Furyl 0 1638 2-Cl- Me 2-Furyl 0 pyridin-3-yl 1639 5-CF₃- Me 2-Furyl 1 pyridin-2-yl 1640 5-Cl- Me 2-Furyl 1 pyridin-2-yl 1641 C₆H₅ Me 3-Me-isothiazol-5-yl 1 1642 2-Cl—C₆H₄ Me Isothiazol-5-yl 1 1643 3-Cl—C₆H₄ Me Isothiazol-5-yl 1 1644 4-Cl—C₆H₄ Me 3-Me-isothiazol-5- 1 1645 2-Me—C₆H₄ Me 3-Me-isothiazol-5-yl 1 1646 3-Me—C₆H₄ Me Isothiazol-5-yl 1 1647 4-Me—C₆H₄ Me Isothiazol-5-yl 1 1648 2-MeO—C₆H₄ Me Isothiazol-5-yl 1 1649 4-Br—C₆H₄ Me Isothiazol-5-yl 1 1650 3-CF₃—C₆H₄ Me Isothiazol-5-yl 1 1651 2,4-Cl₂—C₆H₃ Me Isothiazol-5-yl 1 1652 2,5-Cl₂—C₆H₃ Me Isothiazol-5-yl 1 1653 2,4-Me₂—C₆H₃ Me Isothiazol-5-yl 1 1654 2,5-Me₂—C₆H₃ Me 3-Me-isothiazol-5-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.23(3H, s), 2.40(3H, s), 4.21 (3H, s), 5.01(2H, s), 6.51(1H, s), 6.60- 6.65(1H, m), 6.71(1H, s), 6.96(1H, d, J=7.9), 7.37- 7.71(4H, m) 1655 C₆H₅ Me Isothiazol-5-yl 0 1656 4-Cl—C₆H₄ Me Isothiazol-5-yl 0 1657 4-Me—C₆H₄ Me Isothiazol-5-yl 0 1658 2-Cl- Me Isothiazol-5-yl 1 pyridin-3-yl 1659 5-CF₃- Me Isothiazol-5-yl 1 pyridin-2-yl 1660 5-Cl- Me Isothiazol-5-yl 1 pyridin-2-yl 1661 C₆H₅ Et Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 1.35(1.28)(3H, t, J=7.3), 4.31(4.26)(2H, q, J=7.3), 5.06(4.98)(2H, s), 6.81- 7.60(10H, m), 8.46(8.38)(1H, d, J=1.8) 1662 2-Cl—C₆H₄ Et Isoxazol-3-yl 1 1663 3-Cl—C₆H₄ Et Isoxazol-3-yl 1 1664 4-Cl—C₆H₄ Et Isoxazol-3-yl 1 1665 2-Me—C₆H₄ Et Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 1.36(1.28)(3H, t, J=7.3), 2.20(2.18)(3H, s), 4.23- 4.37(2H, m), 5.04(4.98)(2, s), 6.68-7.63(9H, m), 8.44(8.38)(1H, d, J=1.8) 1666 3-Me—C₆H₄ Et Isoxazol-3-yl 1 1667 2-Me—C₆H₄ Allyl Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 2.20(2.17)(3H, s), 4.69- 4.78(2H, m), 5.05(4.98)(2H, s), 5.18-5.38(2H, m), 5.92- 6.08(1H, m), 6.69-7.63(9H, m), 8.45(8.38)(1H, d, J=1.8) 1688 2-MeO—C₆H₄ Et Isoxazol-3-yl 1 1669 4-Br—C₆H₄ Et Isoxazol-3-yl 1 1670 3-CF₃—C₆H₄ Et Isoxazol-3-yl 1 1671 2,4-Cl₂—C₆H₃ Et Isoxazol-3-yl 1 1672 2,5-Cl₂—C₆H₃ Et Isoxazol-3-yl 1 1673 2,4-Me₂—C₆H₃ Et Isoxazol-3-yl 1 1674 2,5-Me₂—C₆H₃ Et Isoxazol-3-yl 1 ¹H-NMR(CDCl₃) δ ppm: 1.37(1.29)(3H, t, J=7.3), 2.16(2.13)(3H, s), 2.25(2.22)(3H, s), 4.23- 4.38(2H, m), 5.03(4.96)(2H, s), 6.53-7.64(8H, m), 8.45(8.39)(1H, d, J=1.8) 1675 C₆H₅ Et Isoxazol-3-yl 0 1676 4-Cl—C₆H₄ Et Isoxazol-3-yl 0 1677 4-Me—C₆H₄ Et Isoxazol-3-yl 0 1678 2-Cl- Et Isoxazol-3-yl 1 pyridin-3-yl 1679 5-CF₃- Et Isoxazol-3-yl 1 pyridin-2-yl 1680 5-Cl- Et Isoxazol-3-yl 1 pyridin-2-yl 1681 C₆H₅ Me 1,3,4-Thiadiazol-2-yl 1 1682 2-Cl—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1683 3-Cl—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1684 4-Cl—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1685 2-Me—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1686 3-Me—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1687 4-Me—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1688 2-MeO—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1689 4-Br—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1690 3-CF₃—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 1 1691 2,4-Cl₂—C₆H₃ Me 1,3,4-Thiadiazol-2-yl 1 1692 2,5-Cl₂—C₆H₃ Me 1,3,4-Thiadiazol-2-yl 1 1693 2,4-Me₂—C₆H₃ Me 1,3,4-Thiadiazol-2-yl 1 1694 2,5-Me₂—C₆H₃ Me 1,3,4-Thiadiazol-2-yl 1 1695 C₆H₅ Me 1,3,4-Thiadiazol-2-yl 0 1696 4-Cl—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 0 1697 4-Me—C₆H₄ Me 1,3,4-Thiadiazol-2-yl 0 1698 2-Cl- Me 1,3,4-Thiadiazol-2-yl 1 pyridin-3-yl 1699 5-CF₃- Me 1,3,4-Thiadiazol-2-yl 1 pyridin-2-yl 1700 5-Cl- Me 1,3,4-Thiadiazol-2-yl 1 pyridin-2-yl 1701 C₆H₅ Me Oxazol-2-yl 1 1702 2-Cl—C₆H₄ Me Oxazol-2-yl 1 1703 3-Cl—C₆H₄ Me Oxazol-2-yl 1 1704 4-Cl—C₆H₄ Me Oxazol-2-yl 1 1705 2-Me—C₆H₄ Me Oxazol-2-yl 1 1706 3-Me—C₆H₄ Me Oxazol-2-yl 1 1707 4-Me—C₆H₄ Me Oxazol-2-yl 1 1708 2-MeO—C₆H₄ Me Oxazol-2-yl 1 1709 4-Br—C₆H₄ Me Oxazol-2-yl 1 1710 3-CF₃—C₆H₄ Me Oxazol-2-yl 1 1711 2,4-Cl₂—C₆H₃ Me Oxazol-2-yl 1 1712 2,5-Cl₂—C₆H₃ Me Oxazol-2-yl 1 1713 2,4-Me₂—C₆H₃ Me Oxazol-2-yl 1 1714 2,5-Me₂—C₆H₃ Me Oxazol-2-yl 1 1715 C₆H₅ Me Oxazol-2-yl 0 1716 4-Cl—C₆H₄ Me Oxazol-2-yl 0 1717 4-Me—C₆H₄ Me Oxazol-2-yl 0 1718 2-Cl- Me Oxazol-2-yl 1 pyridin-3-yl 1719 5-CF₃- Me Oxazol-2-yl 1 pyridin-2-yl 1720 5-Cl- Me Oxazol-2-yl 1 pyridin-2-yl 1721 C₆H₅ Me Oxazol-5-yl 1 ¹H-NMR(CDCl₃) δ ppm: 4.00(385),(3H, s), 4.98(4.97)(2H, s), 6.78- 7.66(10H, m), 7.92(1H, s) 1722 2-Cl—C₆H₄ Me Oxazol-5-yl 1 1723 3-Cl—C₆H₄ Me Oxazol-5-yl 1 1724 4-Cl—C₆H₄ Me Oxazol-5-yl 1 mp 71-73° C. 1725 2-Me—C₆H₄ Me Oxazol-5-yl 1 1726 3-Me—C₆H₄ Me Oxazol-5-yl 1 1727 4-Me—C₆H₄ Me Oxazol-5-yl 1 1728 2-MeO—C₆H₄ Me Oxazol-5-yl 1 1729 4-Br—C₆H₄ Me Oxazol-5-yl 1 1730 3-CF₃—C₆H₄ Me Oxazol-5-yl 1 3.99(3H, s), 5.01(2H, s), 6.88(1H, s), 6.94-7.62(8H, m), 7.93(1H, s) 1731 2,4-Cl₂—C₆H₃ Me Oxazol-5-yl 1 1732 2,5-Cl₂—C₆H₃ Me Oxazol-5-yl 1 1733 2,4-Me₂—C₆H₃ Me Oxazol-5-yl 1 1734 2,5-Me₂—C₆H₃ Me Oxazol-5-yl 1 mp 90-91° C. 1735 C₆H₅ Me Oxazol-5-yl 0 mp 76.5-77.5° C. 1736 4-Cl—C₆H₄ Me Oxazol-5-yl 0 1737 4-Me—C₆H₄ Me Oxazol-5-yl 0 1738 2-Cl- Me Oxazol-5-yl 1 pyridin-3-yl 1739 5-CF₃- Me Oxazol-5-yl 1 pyridin-2-yl 1740 5-Cl- Me Oxazol-5-yl 1 pyridin-2-yl 1741 C₆H₅ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1742 2-Cl—C₆H₄ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1743 3-Cl—C₆H₄ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1744 4-Cl—C₆Hhd 4 Me 5,5-Me₂-2- 1 isoxazolin-3-yt 1745 2-Me—C₆H₄ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1746 3-Me—C₆H₄ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1747 4-Me—C₆H₄ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1748 2-MeO—C₆H₄ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1749 4-Br—C₆H₄ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1750 2,5-Me₂—C₆H₃ Et 5,5-Me₂-2- 1 ¹H-NMR(CDCl₃) δ ppm: isoxazolin-3-yl 1.25(1.33)(3H, t, J=7.3), 1.36(1.55)(6H, s), 2.20(2.21(3H, s), 2.27(2.26) (3H, s), 3.03-3.22(2H, m), 4.15-4.27(2H, m), 4.92- 5.08(2H, m), 6.57-7.53(7H, m) 1751 2,4-Cl₂—C₆H₃ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1752 2,5-Cl₂—C₆H₃ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1753 2,4-Me₂—C₆H₃ Me 5,5-Me₂-2- 1 isoxazolin-3-yl 1754 2,5-Me₂—C₆H₃ Me 5,5-Me₂-2- 1 mp 86-89° C. isoxazolin-3-yl 1755 C₆H₅ Me 5,5-Me₂-2- 0 isoxazolin-3-yl 1756 4-Cl—C₆H₄ Me 5,5-Me₂-2- 0 isoxazolin-3-yl 1757 4-Me—C₆H₄ Me 5,5-Me₂-2- 0 isoxazolin-3-yl 1758 2-Cl- Me 5,5-Me₂-2- 1 pyridin-3-yl isoxazolin-3-yl 1759 5-CF₃- Me 5,5-Me₂-2- 1 pyridin-2-yl isoxazolin-3-yl 1760 5-Cl- Me 5,5-Me₂-2- 1 pyridin-2-yl isoxazolin-3-yl 1761 C₆H₅ Et 3-Me-isoxazol-5-yl 1 1762 2-Cl—C₆H₄ Et 3-Me-isoxazol-5-yl 1 1763 3-Cl—C₆H₄ Et 3-Me-isoxazol-5-yl 1 1764 4-Cl—C₆H₄ Et 3-Me-isoxazol-5-yl 1 Isomer A: ¹H-NMR(CDCl₃) δ ppm: 1.38(3H, t, J=7.3), 2.16(3H, s), 2.34(3H, s), 4.37(2H, q, J=7.3), 5.02(2H, s), 6.68-7.63(9H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 1.29(3H, t, J=7.3), 2.18(3H, s), 2.26(3H, s), 4.30(2H, q, J=7.3), 4.97(2H, s), 5.96(1H, s), 6.70-7.67(8H, m) 1765 2-Me—C₆H₄ Et 3-Me-isoxazol-5-yl 1 1766 3-Me—C₆H₄ Et 3-Me-isaxazol-5-yl 1 1767 4-Me—C₆H₄ Et 3-Me-isoxazol-5-yl 1 1768 2-MeO—C₆H₄ Et 3-Me-isoxazol-5-yl 1 1769 4-Br—C₆H₄ Et 3-Me-isoxazol-5-yl 1 1770 3-CF₃—C₆H₄ Et 3-Me-isoxazol-5-yl 1 1771 2,4-Cl₂—C₆H₃ Et 3-Me-isoxazol-5-yl 1 1772 2,5-Cl₂—C₆H₃ Et 3-Me-isoxazol-5-yl 1 1773 2,4-Me₂—C₆H₃ Et 3-Me-isoxazol-5-yl 1 1774 2,5-Me₂—C₆H₃ Et 3-Me-isoxazol-5-yl 1 1775 C₆H₅ Et 3-Me-isoxazol-5-yl 0 1776 4-Cl—C₆H₄ Et 3-Me-isoxazol-5-yl 0 1777 4-Me—C₆H₄ Et 3-Me-isoxazol-5-yl 0 1778 2-Cl- Et 3-Me-isoxazol-5-yl 1 pyridin-3-yl 1779 5-CF₃- Et 3-Me-isoxazol-5-yl 1 pyridin-2-yl 1780 5-Cl- Et 3-Me-isoxazol-5-yl 1 pyridin-2-yl 1781 C₆H₅ Et 1-Me- 1 imidazol-2-yl 1782 2-Cl—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1783 3-Cl—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1784 4-Cl—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1785 2-Me—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1786 3-Me—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1787 4-Me—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1788 2-MeO—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1789 4-Br—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1790 3-CF₃—C₆H₄ Et 1-Me- 1 imidazol-2-yl 1791 2,4-Cl₂—C₆H₃ Et 1-Me- 1 imidazol-2-yl 1792 2,5-Cl₂—C₆H₃ Et 1-Me- 1 imidazol-2-yl 1793 2,4-Me₂—C₆H₃ Et 1-Me- 1 imidazol-2-yl 1794 2,5-Me₂—C₆H₃ Et 1-Me- 1 imidazol-2-yl 1795 C₆H₅ Et 1-Me- 0 imidazol-2-yl 1796 4-Cl—C₆H₄ Et 1-Me- 0 imidazol-2-yl 1797 4-Me—C₆H₄ Et 1-Me- 0 imidazol-2-yl 1798 2-Cl- Et 1-Me- 1 pyridin-3-yl imidazol-2-yl 1799 5-CF₃- Et 1-Me- 1 pyridin-2-yl imidazol-2-yl 1800 5-Cl- Et 1-Me- 1 pyridin-2-yl imidazol-2-yl 1801 Pyridin-2-yl Me 1-Me-2-imidazolin- 0 2-yl 1802 5-Cl- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1803 3-Cl- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1804 6-Cl- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1805 3,5-Cl₂- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1806 5-CF₃- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1807 3-CF₃- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1808 6-CF₃-3-Cl- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1809 5-CF₃-3-Cl- Me 1-Me-2-imidazolin- 0 pyridin-2-yl 2-yl 1810 Benzothiazol- Me 1-Me-2-imidazolin- 0 2-yl 2-yl 1811 Benzoxazol- Me 1-Me-2-imidazolin- 0 2-yl 2-yl 1812 Quinolin-2-yl Me 1-Me-2-imidazolin- 0 2-yl 1813 5-CF₃-1,3,4- Me 1-Me-2-imidazolin- 0 thiadiazol-2-yl 2-yl 1814 Pyrimidin-2-yl Me 1-Me-2-imidazolin- 0 2-yl 1815 6-Cl-pyrimidin-4-yl Me 1-Me-2-imidazolin- 0 2-yl 1816 5-Et-6-Me- Me 1-Me-2-imidazolin- 0 pyrimidin-2-yl 2-yl 1817 6-Cl- Me 1-Me-2-imidazolin- 0 pyrazin-2-yl 2-yl 1818 3,6-Me₂- Me 1-Me-2-imidazolin- 0 pyrazin-2-yl 2-yl 1819 3-Ph- Me 1-Me-2-imidazolin- 0 isoxazol-5-yl 2-yl 1820 5-Me- Me 1-Me-2-tmidazolin- 0 isoxazol-3-yl 2-yl 1821 Pyridin-2-yl Me 2-Oxazolin-2-yl 0 1822 5-Cl- Me 2-Oxazolin-2-yl 0 pyridin-2-yl 1823 3-Cl- Me 2-Oxazolin-2-yl 0 pyridin-2-yl 1824 6-Cl- Me 2-Oxazolin-2-yl 0 pyridin-2-yl 1825 3,5-Cl₂- Me 2-Oxazolin-2-yl 0 ¹H-NMR(CDCl₃) δ ppm: pyridin-2-yl 3.97(4.06)(3H, s), 3.86- 4.29(4H, m), 6.82-7.91(6H, m) 1826 5-CF₃- Me 2-Oxazolin-2-yl 0 ¹H-NMR(CDCl₃) δ ppm: pyridin-2-yl 3.78(2H, t, J=9.8), 3.98(3H, s), 4.16(2H, t, J=9.8), 6.94- 7.87(6H, m), 8.43(1H, brs) 1827 3-CF₃- Me 2-Oxazolin-2-yl 0 pyridin-2-yl 1828 6-CF₃-3-Cl- Me 2-Oxazolin-2-yl 0 pyridin-2-yl 1829 5-CF₃-3-Cl- Me 2-Oxazolin-2-yl 0 ¹H-NMR(CDCl₃) δ ppm: pyridin-2-yl 3.92(2H, t, J=9.8), 3.95(3H, s), 4.28(2H, t, J=9.8), 7.15- 7.95(5H, m), 8.22(1H,brs) 1830 Benzothiazol- Me 2-Oxazolin-2-yl 0 ¹H-NMR(CDCl₃) δ ppm: 2-yl 3.84(2H, t, J=9.8), 4.03(3H, s), 4.25(2H, t, J=9.8), 7.23- 7.74(8H, m) 1831 Benzoxazol- Me 2-Oxazolin-2-yl 0 mp 100-103° C. 2-yl 1832 Quinolin-2-yl Me 2-Oxazolin-2-yl 0 1833 5-CF₃-1,3,4- Me 2-Oxazolin-2-yl 0 thiadiazol-2-yl 1834 Pyrimidin-2-yl Me 2-Oxazolin-2-yl 0 1835 6-Cl-pyrimidin-4-yl Me 2-Oxazolin-2-yl 0 mp 103-105° C. 1836 5-Et-6-Me- Me 2-Oxazolin-2-yl 0 pyrimidin-2-yl 1837 6-Cl- Me 2-Oxazolin-2-yl 0 pyrazin-2-yl 1838 3,6-Me₂- Me 2-Oxazolin-2-yl 0 pyrazin-2-yl 1839 3-Ph- Me 2-Oxazolin-2-yl 0 isoxazol-5-yl 1840 5-Me- Me 2-Oxazolin-2-yl 0 isoxazol-3-yl 1841 Pyridin-2-yl Me 2-Isoxazolin-3-yl 0 1842 5-Cl- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1843 3-Cl- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1844 6-Cl- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1845 3,5-Cl₂- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1846 5-CF₃- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1847 3-CF₃- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1848 6-CF₃-3-Cl- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1849 5-CF₃-3-Cl- Me 2-Isoxazolin-3-yl 0 pyridin-2-yl 1850 Benzothiazol- Me 2-Isoxazolin-3-yl 0 2-yl 1851 Benzoxazol- Me 2-Isoxazolin-3-yl 0 2-yl 1852 Quinolin-2-yl Me 2-Isoxazolin-3-yl 0 1853 5-CF₃-1,3,4- Me 2-Isoxazolin-3-yl 0 thiadiazol-2-yl 1854 Pyrimidin-2-yl Me 2-Isoxazolin-3-yl 0 1855 6-Cl-pyrimidin-4-yl Me 2-Isoxazolin-3-yl 0 1856 5-Et-6-Me- Me 2-Isoxazolin-3-yl 0 pyrimidin-2-yl 1857 6-Cl- Me 2-Isoxazolin-3-yl 0 pyrazin-2-yl 1858 3,6-Me₂- Me 2-Isoxazolin-3-yl 0 pyrazin-2-yl 1859 3-Ph- Me 2-Isoxazolin-3-yl 0 isoxazol-5-yl 1860 5-Me- Me 2-Isoxazolin-3-yl 0 isoxazol-3-yl 1861 Pyridin-2-yl Me 3-Me-isoxazol-5-yl 0 1862 5-Cl- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1863 3-Cl- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1864 6-Cl- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1865 3,5-Cl₂- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1866 5-CF₃- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1867 3-CF₃- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1868 6-CF₃-3-Cl- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1869 5-CF₃-Cl- Me 3-Me-isoxazol-5-yl 0 pyridin-2-yl 1870 Benzothiazol- Me 3-Me-isoxazol-5-yl 0 2-yl 1871 Benzoxazol- Me 3-Me-isoxazol-5-yl 0 2-yl 1872 Quinolin-2-yl Me 3-Me-isoxazol-5-yl 0 1873 5-CF₃1,3,4- Me 3-Me-isoxazol-5-yl 0 thiadiazol-2-yl 1874 Pyrimidin-2-yl Me 3-Me-isoxazol-5-yl 0 1875 6-Cl-pyrimidin-4-yl Me 3-Me-isoxazol-5-yl 0 1876 5-Et-6-Me- Me 3-Me-isoxazol-5-yl 0 pyrimidin-2-yl 1877 6-Cl- Me 3-Me-isoxazol-5-yl 0 pyrazin-2-yl 1878 3,6-Me₂- Me 3-Me-isoxazol-5-yl 0 pyrazin-2-yl 1879 3-Ph- Me 3-Me-isoxazol-5-yl 0 isoxazol-5-yl 1880 5-Me- Me 3-Me-isoxazol-5-yl 0 isoxazol-3-yl 1881 Pyridin-2-yl Me 1-Me- 0 imidazol-2-yl 1882 5-Cl- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1883 3-Cl- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1884 6-Cl- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1885 3,5-Cl₂- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1886 5-CF₃- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1887 3-CF₃- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1888 6-CF₃-3-Cl- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1889 5-CF₃-3-Cl- Me 1-Me- 0 pyridin-2-yl imidazol-2-yl 1890 Benzothiazol- Me 1-Me- 0 2-yl imidazol-2-yl 1891 Benzoxazol- Me 1-Me- 0 2-yl imidazol-2-yl 1892 Quinolin-2-yl Me 1-Me- 0 imidazol-2-yl 1893 5-CF₃-1,3,4- Me 1-Me- 0 thiadiazol-2-yl imidazol-2-yl 1894 Pyrimidin-2-yl Me 1-Me- 0 imidazol-2-yl 1895 6-Cl-pyrimidin-4-yl Me 1-Me- 0 imidazol-2-yl 1896 5-Et-6-Me- Me 1-Me- 0 pyrimidin-2-yl imidazol-2-yl 1897 6-Cl- Me 1-Me- 0 pyrazin-2-yl imidazol-2-yl 1898 3,6-Me₂- Me 1-Me- 0 pyrazin-2-yl imidazol-2-yl 1899 3-Ph- Me 1-Me- 0 isoxazol-5-yl imidazol-2-yl 1900 5-Me- Me 1-Me- 0 isoxazol-3-yl imidazol-2-yl 1901 Pyridin-2-yl Me Isoxazol-3-yl 0 1902 5-Cl- Me Isoxazol-3-yl 0 pyridin-2-yl 1903 3-Cl- Me Isoxazol-3-yl 0 pyridin-2-yl 1904 6-Cl- Me Isoxazol-3-yl 0 pyridin-2-yl 1905 3,5-Cl₂- Me Isoxazol-3-yl 0 pyridin-2-yl 1906 5-CF₃- Me Isoxazol-3-yl 0 pyridin-2-yl 1907 3-CF₃- Me Isoxazol-3-yl 0 pyridin-2-yl 1908 6-CF₃-3-Cl- Me Isoxazol-3-yl 0 pyridin-2-yl 1909 5-CF₃-3-Cl- Me Isoxazol-3-yl 0 pyridin-2-yl 1910 Benzothiazol- Me Isoxazol-3-yl 0 2-yl 1911 Benzoxazol- Me Isoxazol-3-yl 0 2-yl 1912 Quinolin-2-yl Me Isoxazol-3-yl 0 1913 5-CF₃-1,3,4- Me Isoxazol-3-yl 0 thiadiazol-2-yl 1914 Pyrimidin-2-yl Me Isoxazol-3-yl 0 1915 6-Cl-pyrimidin-4-yl Me Isoxazol-3-yl 0 1916 5-Et-6-Me- Me Isoxazol-3-yl 0 pyrimidin-2-yl 1917 6-Cl- Me Isoxazol-3-yl 0 pyrazin-2-yl 1918 3,6-Me₂- Me Isoxazol-3-yl 0 pyrazin-2-yl 1919 3-Ph- Me Isoxazol-3-yl 0 isoxazol-5-yl 1920 5-Me- Me Isoxazol-3-yl 0 isoxazol-3-yl 1921 Pyridin-2-yl Me 5-Me-isoxazol-3-yl 0 1922 5-Cl- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1923 3-Cl- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1924 6-Cl- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1925 3,5-Cl₂- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1926 5-CF₃- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1927 3-CF₃- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1928 6-CF₃-3-Cl- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1929 5-CF₃-3-Cl- Me 5-Me-isoxazol-3-yl 0 pyridin-2-yl 1930 Benzothiazol- Me 5-Me-isoxazol-3-yl 0 2-yl 1931 Benzoxazol- Me 5-Me-isoxazol-3-yl 0 2-yl 1932 Quinolin-2-yl Me 5-Me-isoxazol-3-yl 0 1933 5-CF₃-1,3,4- Me 5-Me-isoxazol-3-yl 0 thiadiazol-2-yl 1934 Pyrimidin-2-yl Me 5-Me-isoxazol-3-yl 0 1935 6-Cl-pyrimidin-4-yl Me 5-Me-isoxazol-3-yl 0 1936 5-Et-6-Me- Me 5-Me-isoxazol-3-yl 0 pyrimidin-2-yl 1937 6-Cl- Me 5-Me-isoxazol-3-yl 0 pyrazin-2-yl 1938 3,6-Me₂- Me 5-Me-isoxazol-3-yl 0 pyrazin-2-yl 1939 3-Ph- Me 5-Me-isoxazol-3-yl 0 isoxazol-5-yl 1940 5-Me- Me 5-Me-isoxazol-3-yl 0 isoxazol-3-yl 1941 Pyridin-2-yl Me 1,2,4-Oxadiazol-3-yl 0 1942 5-Cl- Me 1,2,4-Oxadiazol-3-yl 0 pyridin-2-yl 1943 3-Cl- Me 1,2,4-Oxadiazol-3-yl 0 pyridin-2-yl 1944 6-Cl- Me 1,2,4-Oxadiazol-3-yl 0 pyridin-2-yl 1945 3,5-Cl₂- Me 1,2,4-Oxadiazol-3-yl 0 pyridin-2-yl 1946 5-CF₃- Me 1,2,4-Oxadiazol-3-yl 0 pyridin-2-yl 1947 3-CF₃- Me 1,2,4-Oxadiazol-3-yl 0 pyridin-2-yl 1948 6-CF₃-3-Cl- Me 1,2,4-Oxadiazol-3-yl pyridin-2-yl 1949 5-CF₃-3-Cl- Me 1,2,4-Oxadiazol-3-yl 0 pyridin-2-yl 1950 Benzothiazol- Me 1,2,4-Oxadiazol-3-yl 0 2-yl 1951 Benzoxazol- Me 1,2,4-Oxadiazol-3-yl 0 2-yl 1952 Quinolin-2-yl Me 1,2,4-Oxadiazol-3-yl 0 1953 5-CF₃-1,3,4- Me 1,2,4-Oxadiazol-3-yl 0 thiadiazol-2-yl 1954 Pyrimidin-2-yl Me 1,2,4-Oxadiazol-3-yl 0 1955 6-Cl-pyrimidin-4-yl Me 1,2,4-Oxadiazol-3-yl 0 1956 5-Et-6-Me- Me 1,2,4-Oxadiazol-3-yl 0 pyrimidin-2-yl 1957 6-Cl- Me 1,2,4-Oxadiazol-3-yl 0 pyrazin-2-yl 1958 3,6-Me₂- Me 1,2,4-Oxadiazol-3-yl 0 pyrazin-2-yl 1959 3-Ph- Me 1,2,4-Oxadiazol-3-yl 0 isoxazol-5-yl 1960 5-Me- Me 1,2,4-Oxadiazol-3-yl 0 isoxazol-3-yl 1961 Pyridin-2-yl Me 5-Me-1,2,4- 0 oxadiazol-3-yl 1962 5-Cl- Me 5-Me-1,2,4- 0 pyridin-2-yl oxadiazol-3-yl 1963 3-Cl- Me 5-Me-1 2,4- 0 pyridin-2-yl oxadiazol-3-yl 1964 6-Cl- Me 5-Me-1,2,4- 0 pyridin-2-yl oxadiazol-3-yl 1965 3,5-Cl₂- Me 5-Me-1,2,4- 0 pyridin-2-yl oxadiazol-3-yl 1966 5-CF₃- Me 5-Me-1,2,4- 0 pyridin-2-yl oxadiazol-3-yl 1967 3-CF₃- Me 5-Me-1,2,4- 0 pyridin-2-yl oxadiazol-3-yl 1968 6-CF₃-3-Cl- Me 5-Me-1,2,4- 0 pyridin-2-yl oxadiazol-3-yl 1969 5-CF₃-3-Cl- Me 5-Me-1,2,4- 0 pyridin-2-yl oxadiazol-3-yl 1970 Benzothiazol- Me 5-Me-1,2,4- 0 2-yl oxadiazol-3-yl 1971 Benzoxazol- Me 5-Me-1,2,4- 0 2-yl oxadiazol-3-yl 1972 Quinolin-2-yl Me 5-Me-1,2,4- 0 oxadiazol-3-yl 1973 5-CF₃-1,3,4- Me 5-Me-1,2,4- 0 thiadiazol-2-yl oxadiazol-3-yl 1974 Pyrimidin-2-yl Me 5-Me-1,2,4- 0 oxadiazol-3-yl 1975 6-Cl-pyrimidin-4-yl Me 5-Me-1,2,4- 0 oxadiazol-3-yl 1976 5-Et-6-Me- Me 5-Me-1,2,4- 0 pyrimidin-2-yl oxadiazol-3-yl 1977 6-Cl- Me 5-Me-1,2,4- 0 pyrazin-2-yl oxadiazol-3-yl 1978 3,6-Me₂- Me 5-Me-1,2,4- 0 pyrazin-2-yl oxadiazol-3-yl 1979 3-Ph- Me 5-Me-1,2,4- 0 isoxazol-5-yl oxadiazol-3-yl 1980 5-Me- Me 5-Me-1,2,4- 0 isoxazol-3-yl oxadiazol-3-yl 1981 Pyridin-2-yl Me 1,3,4-Oxadiazol-2-yl 0 1982 5-Cl- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1983 3-Cl- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1984 6-Cl- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1985 3,5-Cl₂- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1986 5-CF₃- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1987 3-CF₃- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1988 6-CF₃-3-Cl- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1989 5-CF₃-3-Cl- Me 1,3,4-Oxadiazol-2-yl 0 pyridin-2-yl 1990 Benzothiazol- Me 1,3,4-Oxadiazol-2-yl 0 2-yl 1991 Benzoxazol- Me 1,3,4-Oxadiazol-2-yl 0 2-yl 1992 Quinolin-2-yl Me 1,3,4-Oxadiazol-2-yl 0 1993 5-CF₃-1,3,4- Me 1,3,4-Oxadiazol-2-yl 0 thiadiazol-2-yl 1994 Pyrimidin-2-yl Me 1,3,4-Oxadiazol-2-yl 0 1995 6-Cl-pyrimidin-4-yl Me 1,3,4-Oxadiazol-2-yl 0 1996 5-Et-6-Me- Me 1,3,4-Oxadiazol-2-yl 0 pyrimidin-2-yl 1997 6-Cl- Me 1,3,4-Oxadiazol-2-yl 0 pyrazin-2-yl 1998 3,6-Me₂- Me 1,3,4-Oxadiazol-2-yl 0 pyrazin-2-yl 1999 3-Ph- Me 1,3,4-Oxadiazol-2-yl 0 isoxazol-5-yl 2000 5-Me- Me 1,3,4-Oxadiazol-2-yl 0 isoxazol-3-yl 2001 C₆H₅ Me 2-Me-2H- 1 mp 63.0-66.0° C. tetrazol-5-yl 2002 2-F—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2003 3-F—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2004 4-F—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2005 2-Cl—C₆H₄ Me 2-Me-2H- 1 mp 122-123° C. tetrazol-5-yl 2006 3-Cl—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2007 4-Cl—C₆H₄ Me 2-Me-2H- 1 mp 120-121.5° C. tetrazol-5-yl 2008 2-Br—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2009 3-Br—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2010 4-Br—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2011 3-I—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2012 2-Me—C₆H₄ Me 2-Me-2H- 1 mp 118-119° C. tetrazol-5-yi 1 2013 3-Me—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2014 4-Me—C₆H₄ Me 2-Me-2H- 1 mp 102.0-103.0° C. tetrazol-5-yl 2015 2-Et—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2016 3-Et—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2017 4-Et—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2018 2-MeO—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2019 3-MeO—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2020 4-MeO—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2021 2-CF₃—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2022 3-CF₃—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2023 4-CF₃—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2024 2,4-F₂—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2025 2,5-F₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2026 2,6-F₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2027 3,4-F₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2028 3,5-F₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2029 2,3-Cl₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2030 2,4-Cl₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2031 2,5-Cl₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2032 3,4-Cl₂—C₆H₃ Me 2-Me-2H- 1 mp 98-99° C. tetrazol-5-yl 2033 3,5-Cl₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2034 2,3-Me₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2035 2,4-Me₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yt 2036 2,5-Me₂—C₆H₃ Me 2-Me-2H- 1 mp 131-132° C. tetrazol-5-yl 2037 3,4-Me₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2038 3,5-Me₂—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2039 2-Cl-4-Me—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2040 2-Cl-5-Me—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2041 4-Cl-2-Me—C₆H₃ Me 2-Me-2H- 1 mp 135-136.5° C. tetrazol-5-yl 2042 4-Cl-3-Me—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2043 3-Ph—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2044 4-Ph—C₆H₄ Me 2-Me-2H- 1 mp 108.0-110.0° C. tetrazol-5-yl 2045 3-i-PrO—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2046 3-i-Pr—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2047 4-i-Pr—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2048 3-t-Bu—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2049 2-MeS—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2050 4-MeS—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2051 2,3,6-F₃—C₆H₂ Me 2-Me-2H- 1 tetrazol-5-yl 2052 2,4,5-Cl₃—C₆H₂ Me 2-Me-2H- 1 tetrazol-5-yl 2053 3-PhO—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2054 3,4,5-(MeO)₃—C₆H₂ Me 2-Me-2H- 1 tetrazol-5-yl 2055 2,3,5-Me₃—C₆H₂ Me 2-Me-2H- 1 tetrazol-5-yl 2056 3,4,5-Me₃—C₆H₂ Me 2-Me-2H- 1 tetrazol-5-yl 2057 C₆F₅ Me 2-Me-2H- 1 tetrazol-5-yl 2058 4-Cl-3-Et—C₆H₃ Me 2-Me-2H- 1 tetrazol-5-yl 2059 3-EtO—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2060 4-EtO—C₆H₄ Me 2-Me-2H- 1 tetrazol-5-yl 2061 C₆H₅ Me 2-Me-2H- 0 tetrazol-5-yl 2062 4-F—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2063 3-Cl—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2064 4-Cl—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2065 3-Me—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2066 4-Me—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2067 4-Et—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2068 4-NO₂—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2069 3,4-Cl₂—C₆H₃ Me 2-Me-2H- 0 tetrazol-5-yl 2070 3,5-Cl₂—C₆H₃ Me 2-Me-2H- 0 tetrazol-5-yl 2071 3,4-Me₂—C₆H₃ Me 2-Me-2H- 0 tetrazol-5-yl 2072 3,5-Me₂—C₆H₃ Me 2-Me-2H- 0 tetrazol-5-yl 2073 3-PhO—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2074 4-Cl-3-Et—C₆H₃ Me 2-Me-2H- 0 tetrazol-5-yl 2075 3-EtO—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2076 3-CF₃—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2077 4-CF₃—C₆H₄ Me 2-Me-2H- tetrazol-5-yl 2078 3-i-PrO—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2079 3-i-Pr—C₆H₄ Me 2-Me-2H- 0 tetrazol-5-yl 2080 4-Cl-3-Me—C₆H₃ Me 2-Me-2H- 0 tetrazol-5-yl 2081 Pyridin-2-yl Me 2-Me-2H- 1 tetrazol-5-yl 2082 Pyridin-3-yl Me 2-Me-2H- 1 tetrazol-5-yl 2083 5-Cl- Me 2-Me-2H- 1 pyridin-2-yl tetrazol-5-yl 2084 3-Cl- Me 2-Me-2H- 1 pyridin-2-yl tetrazol-5-yl 2085 6-Cl- Me 2-Me-2H- 1 pyridin-2-yl tetrazol-5-yl 2086 2-Cl- Me 2-Me-2H- 1 pyridin-3-yl tetrazol-5-yl 2087 5-CF₃- Me 2-Me-2H- 1 pyridin-2-yl tetrazol-5-yl 2088 3-CF₃- Me 2-Me-2H- 1 pyridin-2-yl tetrazol-5-yl 2089 6-CF₃-3-Cl- Me 2-Me-2H- 1 pyridin-2-yl tetrazol-5-yl 2090 5-CF₃-3-Cl- Me 2-Me-2H- 1 pyridin-2-yl tetrazol-5-yl 2091 Benzothiazol- Me 2-Me-2H- 1 2-yl tetrazol-5-yl 2092 Benzoxazol- Me 2-Me-2H- 1 2-yl tetrazol-5-yl 2093 Quinolin-2-yl Me 2-Me-2H- 1 tetrazol-5-yl 2094 5-CF₃-1,3,4- Me 2-Me-2H- 1 thiadiazol-2-yt tetrazol-5-yl 2095 Pyrimidin-2-yl Me 2-Me-2H- 1 tetrazol-5-yl 2096 5-Cl-6-Me- Me 2-Me-2H- 1 pyrimidin-4-yl tetrazol-5-yl 2097 5-Et-6-Me- Me 2-Me-2H- 1 pyrimidin-4-yl tetrazol-5-yl 2098 6-Cl- Me 2-Me-2H- 1 pyrazin-2-yl tetrazol-5-yl 2099 3,6-Me₂- Me 2-Me-2H- 1 pyrazin-2-yl tetrazol-5-yl 2100 5-Me- Me 2-Me-2H- 1 isoxazol-3-yl tetrazol-5-yl No R¹ R³ R⁴ n Physical data 2101 C₆H₅ 1,2,4-Oxadiazol-3-yl 5-Cl 1 2102 2-Cl—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-Cl 1 2103 2-Me—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-Cl 1 2104 2,5-Me₂—C₆H₃ 1,2,4-Oxadiazol-3-yl 5-Cl 1 2105 4-Cl-2-Me—C₆H₃ 1,2,4-Oxadiazol-3-yl 5-Cl 1 2106 4-Cl—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-Cl 0 2107 4-Me—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-Cl 0 2108 C₆H₅ 1,2,4-Oxadiazol-3-yl 5-Cl 0 2109 5-CF₃- 1,2,4-Oxadiazol-3-yl 5-Cl 1 pyridin-2-yl 2110 5-CF₃- 1,2,4-Oxadiazol-3-yl 5-Cl 0 pyridin-2-yl 2111 C₆H₅ 5-Me-1,2,4- 5-Cl 1 oxadiazol-3-yl 2112 2-Cl—C₆H₄ 5-Me-1,2,4- 5-Cl 1 oxadiazol-3-yl 2113 2-Me—C₆H₄ 5-Me-1,2,4- 5-Cl 1 oxadiazol-3-yl 2114 2,5-Me₂—C₆H₃ 5-Me-1,2,4- 5-Cl 1 oxadiazol-3-yl 2115 4-Cl-2-Me—C₆ _(H3) 5-Me-1,2,4- 5-Cl 1 oxadiazol-3-yl 2116 4-Cl—C₆H₄ 5-Me-1,2,4- 5-Cl 0 oxadiazol-3-yl 2117 4-Me—C₆H₄ 5-Me-1,2,4- 5-Cl 0 oxadiazol-3-yl 2118 C₆H₅ 5-Me-1,2,4- 5-Cl 0 oxadiazol-3-yl 2119 5-CF₃- 5-Me-1,2,4- 5-Cl 1 pyridin-2-yl oxadiazol-3-y 2120 5-CF₃- 5-Me-1,2,4- 5-Cl 0 ¹H-NMR(CDCl₃) δ ppm: pyridin-2-yl oxadiazol-3-yl 2.46(3H, s), 4.03(3H, s), 6.77(1H, d, J=9.2), 7.16(1H, d, J=9.2), 7.44-7.86(3H, m), 8.36(1H, d, J=1.8) 2121 C₆H₅ Isoxazol-3-yl 5-Cl 1 2122 2-Cl—C₆H₄ Isoxazol-3-yl 5-Cl 1 2123 2-Me—C₆H₄ Isoxazol-3-yl 5-Cl 1 2124 2,5-Me₂—C₆H₃ Isoxazol-3-yl 5-Cl 1 2125 4-Cl-2-Me—C₆H₃ Isoxazol-3-yl 5-Cl 1 2126 4-Cl—C₆H₄ Isoxazol-3-yl 5-Cl 0 2127 4-Me—C₆H₄ Isoxazol-3-yl 5-Cl 0 2128 C₆H₅ Isoxazol-3-yl 5-Cl 0 2129 5-CF₃- Isoxazol-3-yl 5-Cl 1 pyridin-2-yl 2130 5-CF₃- Isoxazol-3-yl 5-Cl 0 pyridin-2-yl 2131 C₆H₅ 3-Me- 5-Cl 1 isoxazol-5-yl 2132 2-Cl—C₆H₄ 3-Me- 5-Cl 1 isoxazol-5-yl 2133 2-Me—C₆H₄ 3-Me- 5-Cl 1 isoxazol-5-yl 2134 2,5-Me₂—C₆H₃ 3-Me- 5-Cl 1 isoxazol-5-yl 2135 4-Cl-2-Me—C₆H₃ 3-Me- 5-Cl- 1 isoxazol-5-yl 2136 4-Cl—C₆H₄ 3-Me- 5-Cl 0 isoxazol-5-yl 2137 4-Me—C₆H₄ 3-Me- 5-Cl 0 isoxazol-5-yl 2138 C₆H₅ 3-Me- 5-Cl 0 isoxazol-5-yl 2139 5-CF₃- 3-Me- 5-Cl 1 pyridin-2-yl isoxazol-5-yl 2140 5-CF₃- 3-Me- 5-Cl 0 pyridin-2-yl isoxazol-5-yl 2141 C₆H₅ 1-Me-imidazol-2-yl 5-Cl 1 2142 2-Cl—C₆H₄ 1-Me-imidazol-2-yl 5-Cl 1 2143 2-Me—C₆H₄ 1-Me-imidazol-2-yl 5-Cl 1 2144 2,5-Me₂—C₆H₃ 1-Me-imidazol-2-yl 5-Cl 1 2145 4-Cl-2-Me—C₆H₃ 1-Me-imidazol-2-yl 5-Cl 1 2146 4-Cl—C₆H₄ 1-Me-imidazol-2-yl 5-Cl 0 2147 4-Me—C₆H₄ 1-Me-imidazol-2-yl 5-Cl 0 2148 C₆H₅ 1-Me-imidazol-2-yl 5-Cl 0 2149 5-CF₃- 1-Me-imidazol-2-yl 5-Cl 1 pyridin-2-yl 2150 5-CF₃- 1-Me-imidazol-2-yl 5-Cl 0 pyridin-2-yl 2151 C₆H₅ 1-Me-imidazol-2-yl 5-F 1 2152 2-Cl—C₆H₄ 1-Me-imidazol-2-yl 5-F 1 2153 2-Me—C₆H₄ 1-Me-imidazol-2-yl 5-F 1 2154 2,5-Me₂—C₆H₃ 1-Me-imidazol-2-yl 5-F 1 2155 4-Cl-2-Me—C₆H₃ 1-Me-imidazol-2-yl 5-F 1 2156 4-Cl—C₆H₄ 1-Me-imidazol-2-yl 5-F 0 2157 4-Me—C₆H₄ 1-Me-imidazol-2-yl 5-F 0 2158 C₆H₅ 1-Me-imidazol-2-yl 5-F 0 2159 5-CF₃- 1-Me-imidazol-2-yl 5-F 1 pyridin-2-yl 2160 5-CF₃- 1-Me-imidazol-2-yl 5-F 0 pyridin-2-yl 2161 C₆H₅ 1,2,4-Oxadiazol-3-yl 5-F 1 2162 2-Cl—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-F 1 2163 2-Me—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-F 1 2164 2,5-Me₂—C₆H₃ 1,2,4-Oxadiazol-3-yl 5-F 1 2165 4-Cl-2-Me—C₆H₃ 1,2,4-Oxadiazol-3-yl 5-F 1 2166 4-Cl—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-F 0 2167 4-Me—C₆H₄ 1,2,4-Oxadiazol-3-yl 5-F 0 2168 C₆H₅ 1,2,4-Oxadiazol-3-yl 5-F 0 2169 5-CF₃- 1,2,4-Oxadiazol-3-yl 5-F 1 pyridin-2-yl 2170 5-CF₃- 1,2,4-Oxadiazol-3-yl 5-F 0 pyridin-2-yl 2171 C₆H₅ 5-Me-1,2,4- 5-F 1 oxadiazol-3-yl 2172 2-Cl—c₆H₄ 5-Me-1,2,4- 5-F 1 oxadiazol-3-yl 2173 2-Me—C₆H₄ 5-Me-1,2,4- 5-F 1 oxadiazol-3-yl 2174 2,5-Me₂—C₆H₃ 5-Me-1,2,4- 5-F 1 oxadiazoi-3-yl 2175 4-Cl-2-Me—C₆H₃ 5-Me-1,2,4- 5-F 1 oxadiazol-3-yl 2176 4-Cl—C₆H₄ 5-Me-1,2,4- 5-F 0 oxadiazol-3-yl 2177 4-Me—C₆H₄ 5-Me-1,2,4- 5-F 0 oxadiazol-3-yi 2178 C₆H₅ 5-Me-1,2,4- 5-F 0 oxadiazol-3-yl 2179 5-CF₃- 5-Me-1,2,4- 5-F 1 pyridin-2-yl oxadiazol-3-yl 2180 5-CF₃- 5-Me-1,2,4- 5-F 0 pyridin-2-yl oxadiazol-3-yl 2181 C₆H₅ Isoxazol-3-yl 5-F 1 2182 2-Cl—C₅H₄ Isoxazol-3-yl 5-F 1 2183 2-Me—C₆H₄ Isoxazol-3-yl 5-F 1 2184 2,5-Me₂—C₆H₃ Isoxazol-3-yl 5-F 1 2185 4-Cl-2-Me—C₆H₃ Isoxazol-3-yl 5-F 1 2186 4-Cl—C₆H₄ Isoxazol-3-yl 5-F 0 2187 4-Me—C₆H₄ Isoxazol-3-yl 5-F 0 2188 C₆H₅ Isoxazol-3-yl 5-F 0 2189 5-CF₃- Isoxazol-3-yl 5-F 1 pyridin-2-yl 2190 5-CF₃- Isoxazol-3-yl 5-F 1 pyridin-2-yl 2191 C₆H₅ 3-Me- 5-F 1 isoxazol-5-yl 2192 2-Cl—C₆H₄ 3-Me- 5-F 1 isoxazol-5-yl 2193 2-Me—C₆H₄ 3-Me- 5-F 1 isoxazol-5-yl 2194 2,5-Me₂—C₆H₃ 3-Me- 5-F 1 isoxazol-5-yl 2195 4-Cl-2-Me—C₆H₃ 3-Me- 5-F 1 isoxazol-5-yl 2196 4-Cl—C₆H₄ 3-Me- 5-F 0 Isoxazol-5-yl 2197 4-Me—C₆H₄ 3-Me- 5-F 0 isoxazol-5-yl 2198 C₆H₅ 3-Me- 5-F 0 isoxazol-5-yl 2199 5-CF₃- 3-Me- 5-F 1 pyridin-2-yl isoxazol-5-yl 2200 5-CF₃- 3-Me- 5-F 0 pyridin-2-yl isoxazol-5-yl 2201 C₆H₅ 5-Me-1,3,4- H 1 oxadiazol-2-yl 2202 2-Cl—C₆H₄ 5-Me-1,3,4- H 1 oxadiazol-2-yl 2203 4-Cl—C₆H₄ 5-Me-1,3,4- H 1 oxadiazol-2-yl 2204 2-Me—C₆H₄ 5-Me-1,3,4- H 1 oxadiazol-2-yl 2205 4-Me—C₆H₄ 5-Me-1,3,4- H 1 oxadiazol-2-yl 2206 3-CF₃—C₆H₄ 5-Me-1,3,4- H 1 oxadiazol-2-yl 2207 2,5-Me₂—C₆H₃ 5-Me-1,3,4- H 1 mp 134.0-139.0° C. oxadiazol-2-yl 2208 4-Cl-2-Me—C₆H₃ 5-Me-1,3,4- H 1 ¹H-NMR(CDCl₃) δ ppm 2.12(3H, oxadiazol-2-yl s), 2.58(3H, s), 4.05(3H, s), 4.97(2H, s), 6.63(1H, d, J=8.5), 6.99-7.64(6H, m) 2209 2,5-Cl₂—C₆H₃ 5-Me-1,3,4- H 1 oxadiazol-2-yl 2210 5-CF₃- 5-Me-1,3,4- H 1 pyridin-2-yl oxadiazol-2-yl 2211 C₆H₅ Thiazolidin-2-yl H 1 2212 2-Cl—C₆H₄ Thiazolidin-2-yl H 1 2213 4-Cl—C₆H₄ Thiazolidin-2-yl H 1 2214 2-Me—C₆H₄ Thiazolidin-2-yl H 1 2215 4-Me—C₆H₄ Thiazolidin-2-yl H 1 2216 3-CF₃—C₆H₄ Thiazolidin-2-yl 1 I 2217 2,5-Me₂—C₆H₃ Thiazolidin-2-yl H 1 ¹H-NMR(CDCl₃) δ ppm 2.28(6H, s), 2.40(1H, brs), 2.81-3.06(3H, m), 3.38-3.55(1H, m), 3.87(3H, s), 4.85-5.50(3H, m), 6.67-7.64(7H, m) 2218 4-Cl-2-Me—C₆H₃ Thiazolidin-2-yl H 1 2219 2,5-Cl₂₋—C₆H₃ Thiazolidin-2-yl H 1 mp 121.0-122.0° C. 2220 5-CF₃- Thiazolidin-2-yl H 1 pyridin-2-yl 2221 C₆H₅ 3,5-Me₂- H 1 ¹H-NMR(CDCl₃) δppm: isoxazol-4-yl 2.00(1.96)(3H, s), 2.17(3H, s), 3.94(3.91)(3H, s), 5.19(4.94)(2H, s), 6.83-7.66(9H, m) 2222 2-Cl—C₆H₄ 3,5-Me₂- H 1 isoxazol-4-yl 2223 4-Cl—C₆H₄ 3,5-Me₂- H 1 isoxazol-4-yl 2224 2-Me—C₆H₄ 3,5-Me₂- H 1 isaxazol-4-yl 2225 4-Me—C₆H₄ 3,5-Me₂- H 1 isoxazol-4-yl 2226 3-CF₃—C₆H₄ 3,5-Me₂- H 1 isoxazol-4-yl 2227 2,5-Me₂—C₆H₃ 3,5-Me₂- H 1 1~NMR(CDCI3) 8 ppm:1.95- isoxazol-4-yl 2.28(12H, m), 3.94(3.99)(3H, s), 4.93(5.18)(2H, s), 6.57-7.71 (7H, m) 2228 4-Cl-2-Me—C₆H₃ 3,5-Me₂- H 1 ¹H-NMR(CDCl₃) δ ppm: isoxazol-4-yl 1.95(1.98)(3H, s), 2.13--2.23(6H, m), 3.93(3.98)(3H, s), 4.91(5.17)(2H, s), 6.65-6.72(2H, m), 7.01-7.66(5H, m) 2229 2,5-Cl₂—C₆H₃ 3,5-Me₂- H 1 isoxazol-4-yl 2230 5-CF₃- 3,5-Me₂- H 1 pyridin-2-yl isoxazol-4-yl 2231 C₆H₅ 1,3-Dioxolan-2-yl H 1 2232 2-Cl—C₆H₄ 1,3-Dioxolan-2-yl H 1 2233 4-Cl—C₆H₄ 1,3-Dioxolan-2-yl H 1 2234 2-Me—C₆H₄ 1,3-Dioxolan-2-yl H 1 2235 4-Me—C₆H₄ 1,3-Dioxolan-2-yl H 1 2236 3-CF₃—C₆H₄ 1,3-Dioxolan-2-yl H 1 2237 2,5-Me₂—C₆H₃ 1,3-Dioxolan-2-yl H 1 ¹H-NMR(CDCl₃) δ ppm 2.28(3H, s), 2.29(3H, s), 3.59-3.85(4H, m), 3.92(3H, s), 5.04(1H, s), 5.09(1H, s), 5.63(1H, s), 6.66-7.62(7H, m) 2238 4-Cl-2-Me—C₆H₃ 1,3-Dioxolan-2-yl H 1 2239 2,5-Cl₂—C₆H₃ 1,3-Dioxolan-2-yl H 1 2240 5-CF₃- 1,3-Dioxolan-2-yl H 1 pyridin-2-yl 2241 C₆H₅ 3-Me-2-isoxazolin- H 1 5-yl 2242 2-Cl—C₆H₄ 3-Me-2-isoxazolin- H 1 5-yl 2243 4-Cl—C₆H₄ 3-Me-2-isoxazolin- H 1 5-yl 2244 2-Me—C₆H₄ 3-Me-2-isoxazolin- H 1 ¹H-NMR(CDCl₃) δ ppm: 5-yl 1.88(3H, s), 2.26(2.27)(3H, s), 2.84-3.38(2H, m), 3.95(3.87)(3H, s), 4.87-5.38(2H, m), 5.74- 5.81(1H, m), 6.84-6.89(2H, m), 7.11-7.60(6H, m) 2245 4-Me—C₆H₄ 3-Me-2-isoxazolin- H 1 5-yl 2246 3-CF₃—C₆H₄ 3-Me-2-isoxazolin- H 1 5-yl 2247 2,5-Me₂—C₆H₃ 3-Me-2-isoxazolin- H 1 1~NMR(CDCI3) & ppm: 5-yl 1.88(3H, s), 2.20(2.22)(3H, s), 2.30(3H, s), 2.84-3.37(2H, m), 3.96(3.88)(3H, s), 4.85-5.35(2H, m), 5.74-5.82(1H, m), 6.67- 6.69(2H, m), 7.01(5H, m) 2248 4-Cl-2-Me—C₆H₃ 3-Me-2-isoxazolin- H 1 5-yl 2249 2,5-Cl₂—C₆H₃ 3-Me-2-isoxazolin- H 1 5-yl 2250 5-CF₃- 3-Me-2-isoxazolin- H 1 pyridin-2-yl 5-yl 2251 C₆H₅ 4-Me-1,2,3- H 1 mp 90.5-91.5° C. thiadiazol-5-yl 2252 2-Cl—C₆H₄ 4-Me-1,2,3- H 1 thiadiazol-5-yl 2253 4-Cl—C₆H₄ 4-Me-1,2,3- H 1 thiadiazol-5-yl 2254 2-Me—C₆H₄ 4-Me-1,2,3- H 1 thiadiazol-5-yl 2255 4-Me—C₆H₄ 4-Me-1,2,3- H 1 thiadiazol-5-yl 2256 3-CF₃—C₆H₄ 4-Me-1,2,3- H 1 thiadiazol-5-yl 2257 2,5-Me₂—C₆H₃ 4-Me-1,2,3- H 1 ¹H-NMR(CDCl₃) δ ppm: thiadiazol-5-yl 2.01(3H, s), 2.14(3H, s), 2.25(3H, s), 4.18(3H, s), 4.98(2H, s), 6.51(1H, s), 6.65(1H, d, J=7.9), 6.96(1H, d, J=7.3), 7.24-7.96(4H, m) 2258 4-Cl-2-Me—C₆H₃ 4-Me-1,2,3- H 1 thiadiazol-5-yl 2259 2,5-Cl₂—C₆H₃ 4-Me-1,2,3- H 1 thiadiazol-5-yl 2260 5-CF₃- 4-Me-1,2,3- H 1 pyridin-2-yl thiadiazol-5-yl 2261 3,5-Cl₂- Isoxazol-3-yl H 0 pyridin-2-yl 2262 3,5-Cl₂- Isoxazol-5-yl H 0 pyridin-2-yl 2263 3,5-Cl₂- 5-Me- H 0 pyridin-2-yl isoxazol-3-yl 2264 3,5-Cl₂- 3-Me- H 0 pyridin-2-yl isoxazol-5-yl 2265 3,5-Cl₂- 2-Isoxazolin-3-yl H 0 pyridin-2-yl 2266 3,5-Cl₂- 5-Me-2-isoxazolin- H 0 pyridin-2-yl 3-yl 2267 3,5-Cl₂- 3-Me-2-isoxazolin- H 0 pyridin-2-yl 5-yl 2268 3,5-Cl₂- 2-Furyl H 0 pyridin-2-yl 2269 3,5-Cl₂- Thiazolidin-2-yl H 0 pyridin-2-yl 2270 3,5-Cl₂- 1-Me- H 0 pyridin-2-yl imidazol-2-yl 2271 3,5-Cl₂- 1,2,4-Oxadiazol- H 0 pyridin-2-yl 3-yl 2272 3,5-Cl₂- 5-Me-1,2,4- H 0 pyridin-2-yl oxadiazol-3-yl 2273 3,5-Cl₂- 1,2,4-oxadiazol-5-yl H 0 pyridin-2-yl 2274 3,5-Cl₂- 1,3,4-oxadiazol-2-yl H 0 pyridin-2-yl 2275 3,5-Cl₂- 5-Me-1,3,4 H 0 pyridin-2-yl oxadiazol-2-yl 2276 3,5-Cl₂- Isoxazol-3-yl H 1 mp 136-137° C. pyridin-2-yl 2277 3,5-Cl₂- Isoxazol-5-yl H 1 pyridin-2-yl 2278 3,5-Cl₂- 5-Me- H 1 ¹H-NMR(CDCl₃) δ ppm: 2.34(3H, pyridin-2-yl isoxazol-3-yl s), 3.97(3H, s), 5.32(2H, s), 6.36(1H, s), 7.24-7.85(6H, m). 2279 3,5-Cl₂- 3-Me- H 1 Isomer A: ¹H-NMR(CDCl₃) δ ppm: pyridin-2-yl isoxazol-5-yl 2.35(3H, s), 4.12(3H, s), 5.40(2H, s), 6.95(1H, s), 7.37-7.86(6H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.28(3H, s), 4.03(3H, s), 5.30(2H, s), 6.01(1H, s), 7.21-7.86(6H, s) 2280 3,5-Cl₂- 2-Isoxazolin-3-yl H 1 pyridin-2-yl 2281 3,5-Cl₂- 5-Me-2- H 1 pyridin-2-yl isoxazolin-3-yl 2282 3,5-Cl₂- 3-Me-2- H 1 pyridin-2-yl isoxazolin-5-yl 2283 3,5-Cl₂- 2-Furyl H 1 pyridin-2-yl 2284 3,5-Cl₂- Thiazolidin-2-yl H 1 pyridin-2-yl 2285 3,5-Cl₂- 1-Me- H 1 pyridin-2-yl imidazol-2-yl 2286 3,5-Cl₂- 1,2,4-Oxadiazol- H 1 pyridin-2-yl 3-yl 2287 3,5-Cl₂- 5-Me-1,2,4- H 1 pyridin-2-yl oxadiazol-3-yl 2288 3,5-Cl₂- 1,2,4-Oxadiazol- H 1 pyridin-2-yl 5-yl 2289 3,5-Cl₂- 1,3,4-Oxadiazol- H 1 pyridin-2-yl 2-yl 2290 3,5-Cl₂- 5-Me-1,3,4- H 1 pyridin-2-yl oxadiazol-2-yl 2291 5-Cl-3-CF₃- Isoxazol-3-yl H 0 pyridin-2-yl 2292 5-Cl-3-CF₃- Isoxazol-5-yl H 0 pyridin-2-yl 2293 5-Cl-3-CF₃- 5-Me- H 0 pyridin-2-yl isoxazol-3-yl 2294 5-Cl-3-CF₃- 3-Me- H 0 pyridin-2-yl isoxazol-5-yl 2295 5-Cl-3-CF₃- 2-Isoxazolin-3-yl H 0 pyridin-2-yl 2296 5-Cl-3-CF₃- 5-Me-2-isoxazolin- H 0 pyridin-2-yl 3-yl 2297 5-Cl-3-CF₃- 3-Me-2-isoxazolin- H 0 pyridin-2-yl 5-yl 2298 5-Cl-3-CF₃- 2-Furyl H 0 pyridin-2-yl 2299 5-Cl-3-CF₃- Thiazolidin-2-yl H 0 pyridin-2-yl 2300 5-Cl-3-CF₃- 1-Me- H 0 pyridin-2-yl imidazol-2-yl H 0 2301 5-Cl-3-CF₃- 1,2,4-Oxadiazol- H 0 pyridin-2-yl 3-yl 2302 5-Cl-3-CF₃- 5-Me-1,2,4- H 0 pyridin-2-yl oxadiazol-3-yl 2303 5-Cl-3-CF₃- 1,2,4-Oxadiazol- H 0 pyridin-2-yl 5-yl 2304 5-Cl-3-CF₃- 1,3,4-Oxadiazol- H 0 pyridin-2-yl 2-yl 2305 5-Cl-3-CF₃- 5-Me-1,3,4- H 0 pyridin-2-yl oxadiazol-2-yl 2306 5-Cl-3-CF₃- Isoxazol-3-yl H 1 mp 97.5-98.5° C. pyridin-2-yl 2307 5-Cl-3-CF₃- Isoxazol-5-yl H 1 pyridin-2-yl 2308 5-Cl-3-CF₃- 5-Me- H 1 mp 120-121° C. pyridin-2-yl isoxazol-3-yl 2309 5-Cl-3-CF₃- 3-Me- H 1 Isomer A: ¹H-NMR(CDCl₃) δ ppm: pyridin-2-yl isoxazol-5-yl 2.37(3H, s), 4.14(3H, s), 5.45(2H, s), 6.97(1H, s), 7.36-7.63(4H, m), 7.79(1H, d, J=2.4), 8.09(1H, d, J=2.4) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 2.28(3H, s), 4.04(3H, s), 5.33(2H, s), 6.01(1H, s), 7.20-7.65(4H, m), 7.80(1H, d, J=2.4), 8.08(1H, d, J=2.4) 2310 5-Cl-3-CF₃- 2-Isoxazolin-3-yl H 1 pyridin-2-yl 2311 5-Cl-3-CF₃- 5-Me-2-isoxazolin- H 1 pyridin-2-yl 3-yl 2312 5-Cl-3-CF₃- 3-Me-2-isoxazolin- H 1 pyridin-2-yl 5-yl 2313 5-Cl-3-CF₃- 2-Furyl H 1 pyridin-2-yl 2314 5-Cl-3-CF₃- Thiazolidin-2-yl H 1 pyridin-2-yl 2315 5-Cl-3-CF₃- 1-Me- H 1 pyridin-2-yl imidazol-2-yl 2316 5-Cl-3-CF₃- 1,2,4-Oxadiazol-3-yl H 1 pyridin-2-yl 2317 5-Cl-3-CF₃- 5-Me-1,2,4- H 1 pyridin-2-yl oxadiazol-3-yl 2318 5-Cl-3-CF₃- 1,2,4-Oxadiazol-5-yl H 1 pyridin-2-yl 2319 5-Cl-3-CF₃- 1,3,4-Oxadiazol-2-yl H 1 pyridin-2-yl 2320 5-Cl-3-CF₃- 5-Me-1,3,4- H 1 pyridin-2-yl oxadiazol-2-yl No R³ R⁹ R¹⁰ Physical data 2321 1-Me-imidazol-2-yl 2,4-F₂—C₆H₃ Me 2322 1-Me-imidazol-2-yl 2,5-F₂—C₆H₃ Me 2323 1-Me-imidazol-2-yl 3,4-F₂—C₆H₃ Me 2324 1-Me-imidazol-2-yl 3,5-F₂C₆H₃ Me 2325 1-Me-imidazol-2-yl 2,3-Cl₂—C₆H₃ Me 2326 1-Me-imidazol-2-yl 2,4-Cl₂—C₆H₃ Me 2327 1-Me-imidazol-2-yl 2,5-Cl₂—C₆H₃ Me 2328 1-Me-imidazol-2-yl 3,4-Cl₂—C₆H₃ Me 2329 1-Me-imidazol-2-yl 3,5-Cl₂—C₆H₃ Me 2330 1-Me-imidazol-2-yl 3,4-Me₂—C₆H₃ Me 2331 1-Me-imidazol-2-yl 2,4-Me₂—C₆H₃ Me 2332 1-Me-imidazol-2-yl 3-Ph—C₆H₄ Me 2333 1-Me-imidazol-2-yl 4-Ph—C₆H₄ Me 2334 1-Me-imidazol-2-yl Morpholino Me 2335 1-Me-imidazol-2-yl 2,6-Me₂- Me morpholino 2336 1-Me-imidazol-2-yl C₆H₅ Et 2337 1-Me-imidazol-2-yl 4-F—C₆H₄ Et 2338 1-Me-imidazol-2-yl 4-Cl—C₆H₄ Et 2339 1-Me-imidazol-2-yl 4-Me—C₆H₄ Et 2340 1-Me-imidazol-2-yl 3,4-Cl₂—C₆H₃ Et 2341 1H-1,2,4- C₆H₅ Me Triazol-1-yl 2342 1H-1,2,4- 2-F—C₆H₄ Me Triazol-1-yl 2343 1H-1,2,4- 3-F—C₆H₄ Me Triazol-1-yl 2344 1H-1,2,4- 4-F—C₆H₄ Me Triazol-1-yl 2345 1H-1,2,4- 2-Cl—C₆H₄ Me Triazol-1-yl 2346 1H-1,2,4- 3-Cl—C₆H₄ Me Triazol-1-yl 2347 1H-1,2,4- 4-Cl—C₆H₄ Me Triazol-1-yl 2348 1H-1,2,4- 2-Br—C₆H₄ Me Triazol-1-yl 2349 1H-1,2,4- 3-Br—C₆H₄ Me Triazol-1-yl 2350 1H-1,2,4- 4-Br—C₆H₄ Me Triazol-1-yl 2351 1H-1,2,4- 3-I—C₆H₄ Me Triazol-1-yl 2352 1H-1,2,4- 2-Me-C₆H₄ Me Triazol-1-yl 2353 1H-1,2,4- 3-Me—C₆H₄ Me Triazol-1-yl 2354 1H-1,2,4- 4-Me—C₆H₄ Me Triazol-1-yl 2355 1H-1,2,4- 3-Et—C₆H₄ Me Triazol-1-yl 2356 1H-1,2,4- 4-Et—C₆H₄ Me Triazol-1-yl 2357 1H-1,2,4- 3-MeO—C₆H₄ Me Triazol-1-yl 2358 1H-1,2,4- 4-MeO—C₆H₄ Me Triazol-1-yl 2359 1H-1,2,4- 3-CF₃—C₆H₄ Me Triazol-1-yl 2360 1H-1,2,4- 4-CF₃—C₆H₄ Me Triazol-1-yl 2361 1H-1,2,4- 2,4-F₂—C₆H₃ Me Triazol-1-yl 2362 1H-1,2,4- 2,5-F₂—C₆H₃ Me Triazol-1-yl 2363 1H-1,2,4- 3,4-F₂—C₆H₃ Me Triazol-1-yl 2364 1H-1,2,4- 3,5-F₂—C₆H₃ Me Triazol-1-yl 2365 1H-1,2,4- 2,3-Cl₂—C₆H₃ Me Triazol-1-yl 2366 1H-1,2,4- 2,4-Cl₂—C₆H₃ Me Triazol-1-yl 2367 1H-1,2,4- 2,5-Cl₂—C₆H₃ Me Triazol-1-yl 2368 1H-1,2,4- 3,4-Cl₂—C₆H₃ Me Triazol-1-yl 2369 1H-1,2,4- 3,5-Cl₂—C₆H₃ Me Triazol-1-yl 2370 1H-1,2,4- 3,4-Me₂—C₆H₃ Me Triazol-1-yl 2371 1H-1,2,4- 2,4-Me₂—C₆H₃ Me Triazol-1-yl 2372 1H-1,2,4- 3-Ph—C₆H₄ Me Triazol-1-yl 2373 1H-1,2,4- 4-Ph—C₆H₄ Me Triazol-1-yl 2374 1H-1,2,4- Morpholino Me Triazol-1-yl 2375 1H-1,2,4- 2,6-Me₂- Me Triazol-1-yl morpholino 2376 1H-1,2,4- C₆H₅ Et Triazol-1-yl 2377 1H-1,2,4- 4-F—C₆H₄ Et Triazol-1-yl 2378 1H-1,2,4- 4-Cl—C₆H₄ Et Triazol-1-yl 2379 1H-1,2,4- 4-Me—C₆H₄ Et Triazol-1-yl 2380 1H-1,2,4- 3,4-Cl₂-C₆H₃ Et Triazol-1-yl 2381 Isoxazol-3-yl C₆H₅ Me 2382 Isoxazol-3-yl 2-F—C₆H₄ Me 2383 Isoxazol-3-yl 3-F—C₆H₄ Me 2384 Isoxazol-3-yl 4-F—C₆H₄ Me 2385 Isoxazol-3-yl 2-Cl—C₆H₄ Me 2386 Isoxazol-3-yl 3-Cl—C₆H₄ Me 2387 Isoxazol-3-yl 4Cl—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 4.00(3H, s), 5.13(2H, s), 6.74(1H, d, J=1.7), 7.25-7.55(8H, m), 8.36(1H, d, J=1.7) 2388 Isoxazol-3-yl 2-Br—C₆H₄ Me 2389 Isoxszol-3-yl 3-Br—C₆H₄ Me 2390 Isoxazol-3-yl 4-Br—C₆H₄ Me 2391 Isoxazol-3-yl 3-I—C₆H₄ Me 2392 Isoxazol-3-yl 2-Me—C₆H₄ Me 2393 Isoxazol-3-yl 3-Me—C₆H₄ Me 2394 Isoxazol-3-yl 4-Me—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.05(3H, s), 2.34(3H, s), 4.00(3H, s), 5.13(2H, s), 6.73(1H, d, J=1.7), 7.11-7.57(8H, m), 8.35(1H, d, J=1.7) 2395 Isoxazol-3-yl 3-Et—C₆H₄ Me 2396 Isoxazol-3-yl 4-Et—C₆H₄ Me 2397 Isoxazol-3-yl 3-MeO—C₆H₄ Me 2398 Isoxazol-3-yl 4-MeO—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.05(3H, s), 3.81(3H, s), 4.00(3H, s), 5.12(2H, s), 6.73(1H, d, J=1.7), 6.82-6.86(2H, m), 7.25-7.56(6H, m), 8.35(1H, d, J=1.7) 2399 Isoxazol-3-yl 3-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.07(3H, s), 4.00(3H, s), 5.17(2H, s), 6.74(1H, d, J=1.7). 7.26-7.74(7H, m), 7.82(1H, s), 8.36(1H, d, J=1.7) 2400 Isoxazol-3-yl 4-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.07(3H, s), 4.00(3H, s), 5.16(2H, s), 6.74(1H, d, J=1.8), 7.26-7.67(8H, m), 8.36(1H, d, J=1.8) 2401 Isoxazol-3-yl 2,4-F₂—C₆H₃ Me 2402 Isoxazol-3-yl 2,5-F₂—C₆H₃ Me 2403 Isoxazol-3-yl 3,4-F₂—C₆H₃ Me 2404 Isoxazol-3-yl 3,5-F₂—C₆H₃ Me 2405 Isoxazol-3-yl 2,3-Cl₂—C₆H₃ Me 2406 Isoxazol-3-yl 2,4-Cl₂—C₆H₃ Me 2407 Isoxazol-3-yl 2,5-Cl₂—C₆H₃ Me 2408 Isoxazol-3-yl 3,4-Cl₂—C₆H₃ Me ¹H-NMR(CDCl₃) δ ppm: 2.01 (3H, s), 4.00(3H, s), 5.14(2H, s), 6.75(1H, d, J=1.7), 7.25-7.65(7H, m), 8.36(1H, d, J=1.7) 2409 Isoxazol-3-yl 3,5-Cl₂—C₆H₃ Me 2410 Isoxazol-3-yl 3,4-Me₂—C₆H₃ Me 2411 Isoxazol-3-yl 2,4-Me₂—C₆H₃ Me 2412 Isoxazol-3-yl 3-Ph—C₆H₄ Me 2413 Isoxazol-3-yl 4-Ph—C₆H₄ Me 2414 Isoxazol-3-yl Morpholino Me 2415 Isoxazol-3-yl 2,6-Me₂- Me morpholino 2416 Isoxazol-3-yl C₆H₅ Et 2417 Isoxazol-3-yl 4-F—C₆H₄ Et 2418 Isoxazol-3-yl 4-Cl—C₆H₄ Et 2419 Isoxazol-3-yl 4-Me—C₆H₄ Et 2420 Isoxazol-3-yl 3,4-Cl₂—C₆H₃ Et 2421 5-Me- C₆H₅ Me isoxazol-3-yl 2422 5-Me- 2-F—C₆H₄ Me isoxazol-3-yl 2423 5-Me- 3-F—C₆H₄ Me isoxazol-3-yl 2424 5-Me- 4-F—C₆H₄ Me isoxazol-3-yl 2425 5-Me- 2-Cl—C₆H₄ Me isoxazol-3-yl 2426 5-Me- 3-Cl—C₆H₄ Me isoxazol-3-yl 2427 5-Me- 4-Cl—C₆H₄ Me isoxazol-3-yl 2428 5-Me- 2-Br—C₆H₄ Me isoxazol-3-yl 2429 5-Me- 3-Br—C₆H₄ Me isoxazol-3-yl 2430 5-Me- 4-Br—C₆H₄ Me isoxazol-3-yl 2431 5-Me- 3-I—C₆H₄ Me isoxazol-3-yl 2432 5-Me- 2-Me—C₆H₄ Me isoxazol-3-yl 2433 5-Me- 3-Me—C₆H₄ Me isoxazol-3-yl 2434 5-Me- 4-Me—C₆H₄ Me isoxazol-3-yl 2435 5-Me- 3-Et—C₆H₄ Me isoxazol-3-yl 2436 5-Me- 4-Et—C₆H₄ Me isoxazol-3-yl 2437 5-Me- 3-MeO—C₆H₄ Me isoxazol-3-yl 2438 5-Me- 4-MeO—C₆H₄ Me isoxazol-3-yl 2439 5-Me- 3-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.11(3H, s), 2.40(3H, s) isoxazol-3-yl 3.98(3H, s), 5.17(2H, s), 6.35(1H, d, J=0.7), 7.24-7.76(7H, m), 7.83(1H, s) 2440 5-Me- 4-CF₃—C₆H₄ Me isoxazol-3-yl 2441 5-Me- 2,4-F₂—C₆H₃ Me isoxazol-3-yl 2442 5-Me- 2,5-F₂—C₆H₃ Me isoxazol-3-yl 2443 5-Me- 3,4-F₂—C₆H₃ Me isoxazol-3-yl 2444 5-Me- 3,5-F₂—C₆H₃ Me isoxazol-3-yl 2445 5-Me- 2,3-Cl₂—C₆H₃ Me isoxazol-3-yl 2446 5-Me- 2,4-Cl₂—C₆H₃ Me isoxazol-3-yl 2447 5-Me- 2,5-Cl₂—C₆H₃ Me isoxazol-3-yl 2448 5-Me- 3,4-Cl₂—C₆H₃ Me ¹H-NMR(CDCl₃) δ ppm: 2.05(3H, s), isoxazol-3-yl 2.47(3H, s) 3.98(3H, s), 5.14(2H, s), 6.35(1H, s), 7.23-7.53(6H, m), 7.66(1H, d, J=1.7) 2449 5-Me- 3,5-Cl₂—C₆H₃ Me isoxazol-3-yl 2450 5-Me- 3,4-Me₂—C₆H₃ Me isoxazol-3-yl 2451 5-Me- 2,4-Me₂—C₆H₃ Me isoxazol-3-yl 2452 5-Me- 3-Ph—C₆H₄ Me isoxazol-3-yl 2453 5-Me- 4-Ph—C₆H₄ Me isoxazol-3-yl 2454 5-Me- Morpholino Me isoxazol-3-yl 2455 5-Me- 2,6-Me₂- Me isoxazol-3-yl morpholino 2456 5-Me- C₆H₅ Et isoxazol-3-yl 2457 5-Me- 4-F—C₆H₄ Et isoxazol-3-yl 2458 5-Me- 4-Cl—C₆H₄ Et isoxazol-3-yl 2459 5-Me- 4-Me—C₆H₄ Et isoxazol-3-yl 2460 5-Me- 3,4-Cl₂—C₆H₃ Et isoxazol-3-yl 2461 Isoxazol-5-yl C₆H₅ Me 2462 Isoxazol-5-yl 2-F—C₆H₄ Me 2463 Isoxazol-5-yl 3-F—C₆H₄ Me 2464 Isoxazol-5-yl 4-F—C₆H₄ Me 2465 Isoxazol-5-yl 2-Cl—C₆H₄ Me 2466 Isoxazol-5-yl 3-Cl—C₆H₄ Me 2467 Isoxazol-5-yl 4-Cl—C₆H₄ Me 2468 Isoxazol-5-yl 2-Br—C₆H₄ Me 2469 Isoxazol-5-yl 3-Br—C₆H₄ Me 2470 Isoxazol-5-yl 4-Br—C₆H₄ Me 2471 Isoxazol-5-yl 3-I—C₆H₄ Me 2472 Isoxazol-5-yl 2-Me—C₆H₄ Me 2473 Isoxazol-5-yl 3-Me—C₆H₄ Me 2474 Isoxazol-5-yl 4-Me—C₆H₄ Me 2475 Isoxazol-5-yl 3-Et—C₆H₄ Me 2476 Isoxazol-5-yl 4-Et—C₆H₄ Me 2477 Isoxazol-5-yl 3-MeO—C₆H₄ Me 2478 Isoxazol-5-yl 4-MeO—C₆H₄ Me 2479 Isoxazol-5-yl 3-CF₃—C₆H₄ Me 2480 Isoxazol-5-yl 4-CF₃—C₆H₄ Me 2481 Isoxazol-5-yl 2,4-F₂—C₆H₃ Me 2482 Isoxazol-5-yl 2,5-F₂C₆H₃ Me 2483 Isoxazol-5-yl 3,4-F₂—C₆H₃ Me 2484 Isoxazol-5-yl 3,5-F₂—C₆H₃ Me 2485 Isoxazol-5-yl 2,3-Cl₂—C₆H₃ Me 2486 Isoxazol-5-yl 2,4-Cl₂—C₆H₃ Me 2487 Isoxazol-5-yl 2,5-Cl₂—C₆H₃ Me 2488 Isoxazol-5-yl 3,4-Cl₂—C₆H₃ Me 2489 Isoxazol-5-yl 3,5-Cl₂—C₆H₃ Me 2490 Isoxazol-5-yl 3,4-Me₂—C₆H₃ Me 2491 Isoxazol-5-yl 2,4-Me₂—C₆H₃ Me 2492 Isoxazol-5-yl 3-Ph—C₆H₄ Me 2493 Isoxazol-5-yl 4-Ph—C₆H₄ Me 2494 Isoxazol-5-yl Morpholino Me 2495 Isoxazol-5-yl 2,8-Me₂- Me morpholino 2496 Isoxazol-5-yl C₆H₅ Et 2497 Isoxazol-5-yl 4-F—C₆H₄ Et 2498 Isoxazol-5-yl 4-Cl—C₆H₄ Et 2499 Isoxazol-5-yl 4-Me—C₆H₄ Et 2500 Isoxazol-5-yl 3,4-Cl₂—C₆H₃ Et 2501 3-Me- C₆H₅ Me isoxazol-5-yl 2502 3-Me- 2-F—C₆H₄ Me isoxazol-5-yl 2503 3-Me- 3-F—C₆H₄ Me isoxazol-5-yl 2504 3-Me- 4-F—C₆H₄ Me isoxazol-5-yl 2505 3-Me- 2-Cl—C₆H₄ Me isoxazol-5-yl 2506 3-Me- 3-Cl—C₆H₄ Me isoxazol-5-yl 2507 3-Me- 4-Cl—C₆H₄ Me ¹H-NMR(CDCl₃) δ isoxazol-5-yl ppm: 2.03(3H, S), 2.19(3H, S), 4.03(3H, S), 5.12(2H, S), 5.94(2H, S), 7.19-7.56(8H, m) 2508 3-Me- 2-Br—C₆H₄ Me isoxazol-5-yl 2509 3-Me- 3-Br—C₆H₄ Me isoxazol-5-yl 2510 3-Me- 4-Br—C₆H₄ Me isoxazol-5-yl 2511 3-Me- 3-I—C₆H₄ Me isoxazol-5-yl 2512 3-Me- 2-Me—C₆H₄ Me isoxazol-5-yl 2513 3-Me- 3-Me—C₆H₄ Me isoxazol-5-yl 2514 3-Me- 4-Me—C₆H₄ Me isoxazol-5-yl 2515 3-Me- 3-Et—C₆H₄ Me isoxazol-5-yl 2516 3-Me- 4-Et—C₆H₄ Me isoxazol-5-yl 2517 3-Me- 3-MeO—C₆H₄ Me isoxazol-5-yl 2518 3-Me- 4-MeO—C₆H₄ Me isoxazol-5-yl 2519 3-Me- 3-CF₃—C₆H₄ Me isoxazol-5-yl 2520 3-Me- 4-CF₃—C₆H₄ Me isoxazol-5-yl 2521 3-Me- 2,4-F₂—C₆H₃ Me isoxazol-5-yl 2522 3-Me- 2,5-F₂—C₆H₃ Me isoxazol-5-yl 2523 3-Me- 3,4-F₂—C₆H₃ Me isoxazol-5-yl 2524 3-Me- 3,5-F₂—C₆H₃ Me isoxazol-5-yl 2525 3-Me- 2,3-Cl—C₆H₃ Me isoxazol-5-yl 2526 3-Me- 2,4-Cl₂—C₆H₃ Me isoxazol-5-yl 2527 3-Me- 2,5-Cl₂—C₆H₃ Me isoxazol-5-yl 2528 3-Me- 3,4-Cl₂—C₆H₃ Me mp 84.0-85.0° C. isoxazol-5-yl 2529 3-Me- 3,5-Cl₂—C₆H₃ Me isoxazol-5-yl 2530 3-Me- 3,4-Me₂—C₆H₃ Me isoxazol-5-yl 2531 3-Me- 2,4-Me₂—C₆H₃ Me isoxazol-5-yl 2532 3-Me- 3-Ph—C₆H₄ Me isoxazol-5-yl 2533 3-Me- 4-Ph—C₆H₄ Me isoxazol-5-yl 2534 3-Me- Morpholino Me isoxazol-5-yl 2535 3-Me- 2,6-Me₂- Me isoxazol-5-yl morpholino 2536 3-Me- C₆H₅ Et isoxazol-5-yl 2537 3-Me- 4-F—C₆H₄ Et isoxazol-5-yl 2538 3-Me- 4-Cl—C₆H₄ Et isoxazol-5-yl 2539 3-Me- 4-Me—C₆H₄ Et isoxazol-5-yl 2540 3-Me- 3,4-Cl₂—C₆H₃ Et isoxazol-5-yl 2541 1,3,4-Oxadiazol- C₆H₅ Me 2-yl 2542 1,3,4-Oxadiazol- 2-F—C₆H₄ Me 2-yl 2543 1,3,4-Oxadiazol- 3-F—C₆H₄ Me 2-yl 2544 1,3,4-Oxadiazol- 4-F—C₆H₄ Me 2-yl 2545 1,3,4-Oxadiazol- 2-Cl—C₆H₄ Me 2-yl 2546 1,3,4-Oxadiazol- 3-Cl—C₆H₄ Me 2-yl 2547 1,3,4-Oxadiazol- 4-Cl—C₆H₄ Me 2-yl 2548 1,3,4-Oxadiazol- 2-Br—C₆H₄ Me 2-yl 2549 1,3,4-Oxadiazol- 3-Br—C₆H₄ Me 2-yl 2550 1,3,4-Oxadiazol- 4-Br—C₆H₄ Me 2-yl 2551 1,3,4-Oxadiazol- 3-I—C₆H₄ Me 2-yl 2552 1,3,4-Oxadiazol- 2-Me—C₆H₄ Me 2-yl 2553 1,3,4-Oxadiazol- 3-Me—C₆H₄ Me 2-yl 2554 1,3,4-Oxadiazol- 4-Me—C₆H₄ Me 2-yl 2555 1,3,4-Oxadiazol- 3-Et—C₆H₄ Me 2-yl 2556 1,3,4-Oxadiazol- 4-Et—C₆H₄ Me 2-yl 2557 1,3,4-Oxadiazol- 3-MeO—C₆H₄ Me 2-yl 2558 1,3,4-Oxadiazol- 4-MeO—C₆H₄ Me 2-yl 2559 1,3,4-Oxadiazol- 3-CF₃—C₆H₄ Me 2-yl 2560 1,3,4-Oxadiazol- 4-CF₃—C₆H₄ Me 2-yl 2561 1,3,4-Oxadiazol- 2,4-F₂—C₆H₃ Me 2-yl 2562 1,3,4-Oxadiazol- 2,5-F₂—C₆H₃ Me 2-yl 2563 1,3,4-Oxadiazol- 3,4-F₂—C₆H₃ Me 2-yl 2564 1,3,4-Oxadiazol- 3,5-F₂—C₆H₃ Me 2-yl 2565 1,3,4-Oxadiazol- 2,3-Cl₂—C₆H₃ Me 2-yl 2566 1,3,4-Oxadiazol- 2,4-Cl₂—C₆H₃ Me 2-yl 2567 1,3,4-Oxadiazol- 2,5-Cl₂—C₆H₃ Me 2-yl 2568 1,3,4-Oxadiazol- 3,4-Cl₂—C₆H₃ Me 2-yl 2569 1,3,4-Oxadiazol- 3,5-Cl₂—C₆H₃ Me 2-yl 2570 1,3,4-Oxadiazol- 3,4-Me₂—C₆H₃ Me 2-yl 2571 1,3,4-Oxadiazol- 2,4-Me₂—C₆H₃ Me 2-yl 2572 1,3,4-Oxadiazol- 3-Ph—C₆H₄ Me 2-yl 2573 1,3,4-Oxadiazol- 4-Ph—C₆H₄ Me 2-yl 2574 1,3,4-Oxadiazol- Morpholino Me 2-yl 2575 1,3,4-Oxadiazol- 2,6-Me₂- Me 2-yl morpholino 2576 1,3,4-Oxadiazol- C₆H₅ Et 2-yl 2577 1,3,4-Oxadiazol- 4-F—C₆H₄ Et 2-yl 2578 1,3,4-Oxadiazol- 4-Cl—C₆H₄ Et 2-yl 2579 1,3,4-Oxadiazol- 4-Me—C₆H₄ Et 2-yl 2580 1,3,4-Oxadiazol- 3,4-Cl₂—C₆H₃ Et 2-yl 2581 5-Me-1,3,4- C₆H₅ Me oxadiazol-2-yl 2582 5-Me-1,3,4- 2-F—C₆H₄ Me oxadiazol-2-yl 2583 5-Me-1,3,4- 3-F—C₆H₄ Me oxadiazol-2-yl 2584 5-Me-1,3,4- 4-F—C₆H₄ Me oxadiazol-2-yl 2585 5-Me-1,3,4- 2-Cl—C₆H₄ Me oxadiazol-2-yl 2586 5-Me-1,3,4- 3-Cl—C₆H₄ Me oxadiazol-2-yl 2587 5-Me-1,3,4- 4-Cl—C₆H₄ Me oxadiazol-2-yl 2588 5-Me-1,3,4- 2-Br—C₆H₄ Me oxadiazol-2-yl 2589 5-Me-1,3,4- 3-Br—C₆H₄ Me oxadiazol-2-yl 2590 5-Me-1,3,4- 4-Br—C₆H₄ Me oxadiazol-2-yl 2591 5-Me-1,3,4- 3-I—C₆H₄ Me oxadiazol-2-yl 2592 5-Me-1,3,4- 2-Me—C₆H₄ Me oxadiazol-2-yl 2593 5-Me -1,3,4- 3-Me—C₆H₄ Me oxadiazol-2-yl 2594 5-Me-1,3,4- 4-Me—C₆H₄ Me oxadiazol-2-yl 2595 5-Me-1,3,4- 3-Et—C₆H₄ Me oxadiazol-2-yl 2596 5-Me-1,3,4- 4-Et—C₆H₄ Me oxadiazol-2-yl 2597 5-Me-1,3,4- 3-MeO—C₆H₄ Me oxadiazol-2-yl 2598 5-Me-1,3,4- 4-MeO—C₆H₄ Me oxadiazol-2-yl 2599 5-Me-1,3,4- 3-CF₃—C₆H₄ Me oxadiazol-2-yl 2600 5-Me-1,3,4- 4-CF₃—C₆H₄ Me oxadiazol-2-yl 2601 5-Me-1,3,4- 2,4-F₂—C₆H₃ Me oxadiazol-2-yl 2602 5-Me-1,3,4- 2,5-F₂—C₆H₃ Me oxadiazol-2-yl 2603 5-Me-1,3,4- 3,4-F₂—C₆H₃ Me oxadiazol-2-yl 2604 5-Me-1,3,4- 3,5-F₂—C₆H₃ Me oxadiazol-2-yl 2605 5-Me-1,3,4- 2,3-Cl₂—C₆H₃ Me oxadiazol-2-yl 2606 5-Me-1,3,4- 2,4-Cl₂—C₆H₃ Me oxadiazol-2-yl 2607 5-Me-1,3,4- 2,5-Cl₂—C₆H₃ Me oxadiazol-2-yl 2608 5-Me-1,3,4- 3,4-Cl₂—C₆H₃ Me oxadiazol-2-yl 2609 5-Me-1,3,4- 3,5-Cl₂—C₆H₃ Me oxadiazol-2-yl 2610 5-Me-1,3,4- 3,4-Me₂—C₆H₃ Me oxadiazol-2-yl 2611 5-Me-1,3,4- 2,4-Me₂—C₆H₃ Me oxadiazol-2-yl 2612 5-Me-1,3,4- 3-Ph—C₆H₄ Me oxadiazol-2-yl 2613 5-Me-1,3,4- 4-Ph—C₆H₄ Me oxadiazol-2-yl 2614 5-Me-1,3,4- Morpholino Me oxadiazol-2-yl 2615 5-Me-1,3,4- 2,6-Me₂- Me oxadiazoi-2-yl morpholino 2616 5-Me-1,3,4- C₆H₅ Et oxadiazol-2-yl 2617 5-Me-1,3,4- 4-F—C₆H₄ Et oxadiazol-2-yl 2618 5-Me-1,3,4- 4-Cl—C₆H₄ Et oxadiazol-2-yl 2619 5-Me-1,3,4- 4-Me—C₆H₄ Et oxadiazol-2-yl 2620 5-Me-1,3,4- 3,4-Cl₂—C₆H₃ oxadiazol-2-yl 2621 Oxazol-5-yl C₆H₅ Me mp 92.0-93.5° C. 2622 Oxazol-5-yl 2-F—C₆H₄ Me 2623 Oxazol-5-yl 3-F—C₆H₄ Me 2624 Oxazol-5-yl 4-F—C₆H₄ Me 2625 Oxazol-5-yl 2-Cl—C₆H₄ Me 2626 Oxazol-5-yl 3-Cl—C₆H₄ Me 2627 Oxazol-5-yl 4-Cl—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.02(3H, S), 4.01(3H, S), 5.14(2H, S), 6.82(1H, S), 7.21- 7.58(8H, m), 7.90(1H, S) 2628 Oxazol-5-yl 2-Br—C₆H₄ Me 2629 Oxazol-5-yl 3-Br—C₆H₄ Me 2630 Oxazol-5-yl 4-Br—C₆H₄ Me 2631 Oxazol-5-yl 3-I—C₆H₄ Me 2632 Oxazol-5-yl 2-Me—C₆H₄ Me 2633 Oxazol-5-yl 3-Me—C₆H₄ Me 2634 Oxazol-5-yl 4-Me—C₆H₄ Me 2635 Oxazol-5-yl 3-Et—C₆H₄ Me 2636 Oxazol-5-yl 4-Et—C₆H₄ Me 2637 Oxazol-5-yl 3-MeO—C₆H₄ Me 2638 Oxazol-5-yl 4-MeO—C₆H₄ Me 2639 Oxazol-5-yl 3-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, S), 4.01(3H, S), 5.17(2H, S), 6.83(1H, S), 7.22- 7.26(1H, m), 7.38-7.59(5H, m), 7.72(1H, d, j=7.9), 7.81(1H, S), 7.91(1H, S) 2640 Oxazol-5-yl 4-CF₃—C₆H₄ Me 2641 Oxazol-5-yl 2,4-F₂—C₆H₃ Me 2642 Oxazol-5-yl 2,5-F₂—C₆H₃ Me 2643 Oxazol-5-yl 3,4-F₂—C₆H₃ Me 2644 Oxazol-5-yl 3,5-F₂—C₆H₃ Me 2645 Oxazol-5-yl 2,3-Cl₂—C₆H₃ Me 2646 Oxazol-5-yl 2,4-Cl₂—C₆H₃ Me ¹H-NMR(CDCl₃) δ ppm: 2.02(3H, S), 4.00(3H, S), 5.13(2H, S), 6.85(1H, S), 7.13- 7.58(7H, m)7.91(1H, S) 2647 Oxazol-5-yl 2,5-Cl₂—C₆H₃ Me 2648 Oxazol-5-yl 3,4-Cl₂—C₆H₃ Me mp 94.0-95.0° C. 2649 Oxazol-5-yl 3,5-Cl₂—C₆H₃ Me 2650 Oxazol-5-yl 3,4-Me₂—C₆H₃ Me 2651 Oxazol-5-yl 2,4-Me₂—C₆H₃ Me 2652 Oxazol-5-yl 3-Ph—C₆H₄ Me 2653 Oxazol-5-yl 4-Ph—C₆H₄ Me 2654 Oxazol-5-yl Morpholino Me 2655 Oxazol-5-yl 2,6-Me₂- Me morpholino 2656 Oxazol-5-yl C₆H₅ Et 2657 Oxazol-5-yl 4-F—C₆H₄ Et 2658 Oxazol-5-yl 4-Cl—C₆H₄ Et 2659 Oxazol-5-yl 4-Me—C₆H₄ Et 2660 Oxazol-5-yl 3,4-Cl₂—C₆H₃ Et 2661 5-Me-1,2,4- C₆H₅ Me ¹H-NMR(CDCl₃) δ oxadiazol-3-yl ppm: 2.11(3H, s), 2.95(3H, s), 4.08(3H, s), 5.16(2H, s), 7.26-7.58(9H, m) 2662 5-Me-1,2,4- 2-F—C₆H₄ Me oxadiazol-3-yl 2663 5-Me-1,2,4- 3-F—C₆H₄ Me oxadiazol-3-yl 2664 5-Me-1,2,4- 4-F—C₆H₄ Me oxadiazol-3-yl 2665 5-Me-1,2,4- 2-Cl—C₆H₄ Me oxadiazol-3-yl 2666 5-Me-1,2,4- 3-Cl—C₆H₄ Me oxadiazol-3-yl 2667 5-Me-1,2,4- 4-Cl—C₆H₄ Me oxadiazol-3-yl 2668 5-Me-1,2,4- 2-Br—C₆H₄ Me oxadiazol-3-yl 2669 5-Me-1,2,4- 3-Br—C₆H₄ Me oxadiazol-3-yl 2670 5-Me-1,2,4- 4-Br—C₆H₄ Me oxadiazol-3-yl 2671 5-Me-1,2,4- 3-I—C₆H₄ Me oxadiazol-3-yl 2672 5-Me-1,2,4- 2-Me—C₆H₄ Me oxadiazol-3-yl 2673 5-Me-1,2,4- 3-Me—C₆H₄ Me oxadiazol-3-yl 2674 5-Me-1,2,4- 4-Me—C₆H₄ Me oxadiazol-3-yl 2675 5-Me-1,2,4- 3-Et—C₆H₄ Me oxadiazol-3-yl 2676 5-Me-1,2,4- 4-Et—C₆H₄ Me oxadiazol-3-yl 2677 5-Me-1,2,4- 3-MeO—C₆H₄ Me oxadiazol-3-yl 2678 5-Me-1,2,4- 4-MeO—C₆H₄ Me oxadiazol-3-yl 2679 5-Me-1,2,4- 3-CF₃—C₆H₄ Me oxadiazol-3-yl 2680 5-Me-1,2,4- 4-CF₃—C₆H₄ Me oxadiazol-3-yl 2681 5-Me-1,2,4- 2,4-F₂—C₆H₃ Me oxadiazol-3-yl 2682 5-Me-1,2,4- 2,5-F₂—C₆H₃ Me oxadiazol-3-yl 2683 5-Me-1,2,4- 3,4-F₂—C₆H₃ Me oxadiazol-3-yl 2684 5-Me-1,2,4- 3,5-F₂—C₆H₃ Me oxadiazol-3-yl 2685 5-Me-1,2,4- 2,3-Cl₂—C₆H₃ Me oxadiazol-3-yl 2686 5-Me-1,2,4- 2,4-Cl₂—C₆H₃ Me oxadiazol-3-yl 2687 5-Me-1,2,4- 2,5-Cl₂—C₆H₃ Me oxadiazol-3-yl 2688 5-Me-1,2,4- 3,4-Cl₂—C₆H₃ Me oxadiazol-3-yl 2689 5-Me-1,2,4- 3,5-Cl₂—C₆H₃ Me oxadiazol-3-yl 2690 5-Me-1,2,4- 3,4-Me₂—C₆H₃ Me oxadiazol-3-yl 2691 5-Me-1,2,4- 2,4-Me₂—C₆H₃ Me oxadiazol-3-yl 2692 5-Me-1,2,4- 3-Ph—C₆H₄ Me oxadiazol-3-yl 2693 5-Me-1,2,4- 4-Ph—C₆H₄ Me oxadiazol-3-yl 2694 5-Me-1,2,4- Morpholino Me oxadiazol-3-yl 2695 5-Me-1,2,4- 2,6-Me₂- Me oxadiazol-3-yl morpholino 2696 5-Me-1,2,4- C₆H₅ Et oxadiazol-3-yl 2697 5-Me-1,2,4- 4-F—C₆H₄ Et oxadiazol-3-yl 2698 5-Me-1,2,4- 4-Cl—C₆H₄ Et oxadiazol-3-yl 2699 5-Me-1,2,4- 4-Me—C₆H₄ Et oxadiazol-3-yl 2700 5-Me-1,2,4- 3,4-Cl₂—C₆H₃ Et oxadiazol-3-yl 2701 1-Me-1H- C₆H₅ Me mp 119-120° C. tetrazol-5-yl 2702 1-Me-1H- 2-F—C₆H₄ Me tetrazol-5-yl 2703 1-Me-1H- 3-F—C₆H₄ Me tetrazol-5-yl 2704 1-Me-1H- 4-F—C₆H₄ Me tetrazol-5-yl 2705 1-Me-1H- 2-Cl—C₆H₄ Me tetrazol-5-yl 2706 1-Me-1H- 3-Cl—C₆H₄ Me tetrazol-5-yl 2707 1-Me-1H- 4-Cl—C₆H₄ Me tetrazol-5-yl 2708 1-Me-1H- 2-Br—C₆H₄ Me tetrazol-5-yl 2709 1-Me-1H- 3-Br—C₆H₄ Me tetrazol-5-yl 2710 1-Me-1H- 4-Br—C₆H₄ Me tetrazol-5-yl 2711 1-Me-1H- 3-I—C₆H₄ Me tetrazol-5-yl 2712 1-Me-1H- 2-Me—C₆H₄ Me tetrazol-5-yl 2713 1-Me-1H- 3-Me—C₆H₄ Me tetrazol-5-yl 2714 1-Me-1H- 4-Me—C₆H₄ Me tetrazol-5-yl 2715 1-Me-1H- 3-Et—C₆H₄ Me tetrazol-5-yl 2716 1-Me-1H- 4-Et—C₆H₄ Me tetrazol-5-yl 2717 1-Me-1H- 3-MeO—C₆H₄ Me tetrazol-5-yl 2718 1-Me-1H- 4-MeO—C₆H₄ Me tetrazol-5-yl 2719 1-Me-1H- 3-CF₃—C₆H₄ Me tetrazol-5-yl 2720 1-Me-1H- 4-CF₃—C₆H₄ Me tetrazol-5-yl 2721 1-Me-1H- 2,4-F₂—C₆H₃ Me tetrazol-5-yl 2722 1-Me-1H- 2,5-F₂—C₆H₃ Me tetrazol-5-yl 2723 1-Me-1H- 3,4-F₂—C₆H₃ Me tetrazol-5-yl 2724 1-Me-1H- 3,5-F₂—C₆H₃ Me tetrazol-5-yl 2725 1-Me-1H- 2,3-Cl₂—C₆H₃ Me tetrazol-5-yl 2726 1-Me-1H- 2,4-Cl₂—C₆H₃ Me tetrazol-5-yl 2727 1-Me-1H- 2,5-Cl₂—C₆H₃ Me tetrazol-5-yl 2728 1-Me-1H- 3,4-Cl₂—C₆H₃ Me tetrazol-5-yl 2729 1-Me-1H- 3,5-Cl₂—C₆H₃ Me tetrazol-5-yl 2730 1-Me-1H- 3,4-Me₂—C₆H₃ Me tetrazol-5-yl 2731 1-Me-1H- 2,4-Me₂—C₆H₃ Me tetrazol-5-yl 2732 1-Me-1H- 3-Ph—C₆H₄ Me tetrazol-5-yl 2733 1-Me-1H- 4-Ph—C₆H₄ Me tetrazol-5-yl 2734 1-Me-1H- morpholino Me tetrazol-5-yl 2735 1-Me-1H- 2,6-Me₂- Me tetrazol-5-yl morpholino 2736 1-Me-1H- C₆H₅ Et tetrazol-5-yl 2737 1-Me-1H- 4-F—C₆H₄ Et tetrazol-5-yl 2738 1-Me-1H- 4-Cl—C₆H₄ Et tetrazol-5-yl 2739 1-Me-1H- 4-Me—C₆H₄ Et tetrazol-5-yl 2740 1-Me-1H- 3,4-Cl₂—C₆H₃ Et tetrazol-5-yl 2741 2-Me-2H- C₆H₅ Me mp 96-98° C. tetrazol-5-yl 2742 2-Me-2H- 2-F—C₆H₄ Me tetrazol-5-yl 2743 2-Me-2H- 3-F—C₆H₄ Me tetrazol-5-yl 2744 2-Me-2H- 4-F—C₆H₄ Me tetrazol-5-yl 2745 2-Me-2H- 2-Cl—C₆H₄ Me tetrazol-5-yl 2746 2-Me-2H- 3-Cl—C₆H₄ Me tetrazol-5-yl 2747 2-Me-2H- 4-Cl—C₆H₄ Me tetrazol-5-yl 2748 2-Me-2H- 2-Br—C₆H₄ Me tetrazol-5-yl 2749 2-Me-2H- 3-Br—C₆H₄ Me tetrazol-5-yl 2750 2-Me-2H- 4-Br—C₆H₄ Me tetrazol-5-yl 2751 2-Me-2H- 3-I—C₆H₄ Me tetrazol-5-yl 2752 2-Me-2H- 2-Me—C₆H₄ Me tetrazol-5-yl 2753 2-Me-2H- 3-Me—C₆H₄ Me tetrazol-5-yl 2754 2-Me-2H- 4-Me—C₆H₄ Me tetrazol-5-yl 2755 2-Me-2H- 3-Et—C₆H₄ Me tetrazol-5-yl 2756 2-Me-2H- 4-Et-C₆H₄ Me tetrazol-5-yl 2757 2-Me-2H- 3-MeO—C₆H₄ Me tetrazol-5-yl 2758 2-Me-2H- 4-MeO—C₆H₄ Me tetrazol-5-yl 2759 2-Me-2H- 3-CF₃—C₆H₄ Me tetrazol-5-yl 2760 2-Me-2H- 4-CF₃—C₆H₄ Me tetrazol-5-yl 2761 2-Me-2H- 2,4-F₂—C₆H₃ Me tetrazol-5-yl 2762 2-Me-2H- 2,5-F₂—C₆H₃ Me tetrazol-5-yl 2763 2-Me-2H- 3,4-F₂—C₆H₃ Me tetrazol-5-yl 2764 2-Me-2H- 3,5-F₂—C₆H₃ Me tetrazol-5-yl 2765 2-Me-2H- 2,3-Cl₂—C₆H₃ Me tetrazol-5-yl 2766 2-Me-2H- 2,4-Cl₂—C₆H₃ Me tetrazol-5-yl 2767 2-Me-2H- 2,5-Cl₂—C₆H₃ Me tetrazol-5-yl 2768 2-Me-2H- 3,4-Cl₂—C₆H₃ Me tetrazol-5-yl 2769 2-Me-2H- 3,5-Cl₂—C₆H₃ Me tetrazol-5-yl 2770 2-Me-2H- 3,4-Me₂—C₆H₃ Me tetrazol-5-yl 2771 2-Me-2H- 2,4-Me₂—C₆H₃ Me tetrazol-5-yl 2772 2-Me-2H- 3-Ph—C₆H₄ Me tetrazol-5-yl 2773 2-Me-2H- 4-Ph—C₆H₄ Me tetrazol-5-yl 2774 2-Me-2H- Morpholino Me tetrazol-5-yl 2775 2-Me-2H- 2,6-Me₂- tetrazol-5-yl morpholino 2776 2-Me-2H- C₆H₅ Et tetrazol-5-yl 2777 2-Me-2H- 4-F—C₆H₄ Et tetrazol-5- 2778 2-Me-2H- 4-Cl—C₆H₄ Et tetrazol-5-yl 2779 2-Me-2H- 4-Me—C₆H₄ Et tetrazol-5-yl 2780 2-Me-2H- 3,4-Cl₂—C₆H₃ Et tetrazol-5-yl 2781 Thiazolidin-2-yl C₆H₅ Me 2782 Thiazolidin-2-yl 2-F—C₆H₄ Me 2783 Thiazolidin-2-yl 3-F—C₆H₄ Me 2784 Thiazolidin-2-yl 4-F—C₆H₄ Me 2785 Thiazolidin-2-yl 2-Cl—C₆H₄ Me 2786 Thiazoiidin-2-yl 3-Cl—C₆H₄ Me 2787 Thiazolidin-2-yl 4-Cl—C₆H₄ Me 2788 Thiazolidin-2-yl 2-Br—C₆H₄ Me 2789 Thiazolidin-2-yl 3-Br—C₆H₄ Me 2790 Thiazolidin-2-yl 4-Br—C₆H₄ Me 2791 Thiazolidin-2-yl 3-I—C₆H₄ Me 2792 Thiazolidin-2-yl 2-Me—C₆H₄ Me 2793 Thiazolidin-2-yl 3-Me—C₆H₄ Me 2794 Thiazolidin-2-yl 4-Me—C₆H₄ Me 2795 Thiazolidin-2-yl 3-Et—C₆H₄ Me 2796 Thiazolidin-2-yl 4-Et—C₆H₄ Me 2797 Thiazolidin-2-yl 3-MeO—C₆H₄ Me 2798 Thiazolidin-2-yl 4-MeO—C₆H₄ Me 2799 Thiazolidin-2-yl 3-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.39(3H, S), 2.75-3.10(3H, m)3.50(2H, m), 3.86(3H, S), 5.20-5.30(2H, m), 5.30- 5.50(1H, m), 7.37-7.61(6H, m),7.82(1H, j=7.9), 7.91(1H, S) 2800 Thiazolidin-2-yl 4-CF₃—C₆H₄ Me 2801 Thiazolidin-2-yl 2,4-F₂—C₆H₃ Me 2802 Thiazolidin-2-yl 2,5-F₂—C₆H₃ Me 2803 Thiazolidin-2-yl 3,4-F₂—C₆H₃ Me 2804 Thiazolidin-2-yl 3,5-F₂—C₆H₃ Me 2805 Thiazolidin-2-yl 2,3-Cl₂—C₆H₃ Me 2806 Thiazolidin-2-yl 2,4-Cl₂—C₆H₃ Me 2807 Thiazolidin-2-yl 2,5-Cl₂—C₆H₃ Me 2808 Thiazolidin-2-yl 3,4-Cl₂—C₆H₃ Me 2809 Thiazolidin-2-yl 3,5-Cl₂—C₆H₃ Me 2810 Thiazolidin-2-yl 3,4-Me₂—C₆H₃ Me 2811 Thiazolidin-2-yl 2,4-Me₂—C₆H₃ Me 2812 Thiazolidin-2-yl 3-Ph—C₆H₄ Me 2813 Thiazolidin-2-yl 4-Ph—C₆H₄ Me 2814 Thiazolidin-2-yl Morpholino Me ¹H-NMR(CDCl₃) δ ppm: 1.98(3H, S), 2.70-2.80(1H, m), 2.89-3.06(2H, m), 3.10(4H, t j=4.9), 3.4-3.5(2H, m), 3.69(4H, tj=4.9), 3.83(3H, S), 4.91(2H, S), 5.40(1H, S)7.33-7.55(4H, m) 2815 Thiazolidin-2-yl 2,6-Me₂- Me morpholino 2816 Thiazolidin-2-yl C₆H₅ Et 2817 Thiazolidin-2-yl 4-F—C₆H₄ Et 2818 Thiazolidin-2-yl 4-Cl—C₆H₄ Et 2819 Thiazolidin-2-yl 4-Me—C₆H₄ Et 2820 Thiazolidin-2-yl 3,4-Cl₂—C₆H₃ Et 2821 3-Me-thiazolidin- C₆H₅ Me 2-yl 2822 3-Me-thiazolidin- 2-F—C₆H₄ Me 2-yl 2823 3-Me-thiazolidin- 3-F—C₆H₄ Me 2-yl 2824 3-Me-thiazolidin- 4-F—C₆H₄ Me 2-yl 2825 3-Me-thiazolidin- 2-Cl—C₆H₄ Me 2-yl 2826 3-Me-thiazolidin- 3-Cl—C₆H₄ Me 2-yl 2827 3-Me-thiazolidin- 4-Cl—C₆H₄ Me 2-yl 2828 3-Me-thiazolidin- 2-Br—C₆H₄ Me 2-yl 2829 3-Me-thiazolidin- 3-Br—C₆H₄ Me 2-yl 2830 3-Me-thiazolidin- 4-Br—C₆H₄ Me 2-yl 2831 3-Me-thiazolidin- 3-I—C₆H₄ Me 2-yl 2832 3-Me-thiazolidin- 2-Me—C₆H₄ Me 2-yl 2833 3-Me-thiazolidin- 3-Me—C₆H₄ Me 2-yl 2834 3-Me-thiazolidin- 4-Me—C₆H₄ Me 2-yl 2835 3-Me-thiazolidin- 3-Et—C₆H₄ Me 2-yl 2836 3-Me-thiazolidin- 4-Et—C₆H₄ Me 2-yl 2837 3-Me-thiazolidin- 3-MeO—C₆H₄ Me 2-yt 2838 3-Me-thiazolidin- 4-MeO—C₆H₄ Me 2-yl 2839 3-Me-thiazolidin- 3-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2-yl 2.31(3H, d j=3.7), 2.47(3H, d j=14.7), 2.83-3.25(4H, m), 3.84(3H, S), 4.94((1H, d j=54.9), 5.14-5.35(2H, m), 7.19- 7.80(6H, m), 7.83(1H, d j=7.9), 7.93(1H, S) 2840 3-Me-thiazolidin- 4-CF₃—C₆H₄ Me 2-yl 2841 3-Me-thiazolidin- 2,4-F₂—C₆H₃ Me 2-yl 2842 3-Me-thiazolidin- 2,5-F₂—C₆H₃ Me 2-yl 2843 3-Me-thiazolidin- 3,4-F₂—C₆H₃ Me 2-yl 2844 3-Me-thiazolidin- 3,5-F₂—C₆H₃ Me 2-yl 2845 3-Me-thiazolidin- 2,3-Cl₂—C₆H₃ Me 2-yl 2846 3-Me-thiazolidin- 2,4-Cl₂—C₆H₃ Me 2-yl 2847 3-Me-thiazolidin- 2,5-Cl₂—C₆H₃ Me 2-yl 2848 3-Me-thiazolidin- 3,4-Cl₂—C₆H₃ Me 2-yl 2849 3-Me-thiazolidin- 3,5-Cl₂—C₆H₃ Me 2-yl 2850 3-Me-thiazolidin- 3,4-Me₂—C₆H₃ Me 2-yl 2851 3-Me-thiazolidin- 2,4-Me₂—C₆H₃ Me 2-yl 2852 3-Me-thiazolidin- 3-Ph—C₆H₄ Me 2-yl 2853 3-Me-thiazolidin- 4-Ph—C₆H₄ Me 2-yl 2854 3-Me-thiazolidin- Morpholino Me 2-yl 2855 3-Me-thiazolidin- 2,6-Me₂- Me 2-yl morpholino 2856 3-Me-thiazolidin- C₆H₅ Et 2-yl 2857 3-Me-thiazolidin- 4-F—C₆H₄ Et 2-yl 2858 3-Me-thiazolidin- 4-Cl—C₆H₄ Et 2-yl 2859 3-Me-thiazolidin- 4-Me—C₆H₄ Et 2-yl 2860 3-Me-thiazolidin- 3,4-Cl₂—C₆H₃ Et 2-yl 2861 2-Isoxazolin-3-yl C₆H₅ Me 2862 2-Isoxazolin-3-yl 2-F—C₆H₄ Me 2863 2-Isoxazolin-3-yl 3-F—C₆H₄ Me 2864 2-Isoxazolin-3-yl 4-F—C₆H₄ Me 2865 2-Isoxazolin-3-yl 2-Cl—C₆H₄ Me 2866 2-Isoxazolin-3-yl 3-Cl—C₆H₄ Me 2867 2-Isoxazolin-3-yl 4-Cl—C₆H₄ Me 2868 2-Isoxazolin-3-yl 2-Br—C₆H₄ Me 2869 2-Isoxazolin-3-yl 3-Br—C₆H₄ Me 2870 2-Isoxazolin-3-yl 4-Br—C₆H₄ Me 2871 2-Isoxazolin-3-yl 3-I—C₆H₄ Me 2872 2-Isoxazolin-3-yl 2-Me—C₆H₄ Me 2873 2-Isoxazolin-3-yl 3-Me—C₆H₄ Me 2874 2-Isoxazolin-3-yl 4-Me—C₆H₄ Me 2875 2-Isoxazolin-3-yl 3-Et—C₆H₄ Me 2876 2-Isoxazolin-3-yl 4-Et—C₆H₄ Me 2877 2-Isoxazolin-3-yl 3-MeO—C₆H₄ Me 2878 2-Isoxazolin-3-yl 4-MeO—C₆H₄ Me 2879 2-Isoxazolin-3-yl 3-CF₃—C₆H₄ Me 2880 2-Isoxazolin-3-yl 4-CF₃—C₆H₄ Me 2881 2-Isoxazolin-3-yl 2,4-F₂—C₆H₃ Me 2882 2-Isoxazolin-3-yl 2,5-F₂—C₆H₃ Me 2883 2-Isoxazolin-3-yl 3,4-F₂—C₆H₃ Me 2884 2-Isoxazolin-3-yl 3,5-F₂—C₆H₃ Me 2885 2-Isoxazolin-3-yl 2,3-Cl₂—C₆H₃ Me 2886 2-Isoxazolin-3-yl 2,4-Cl₂—C₆H₃ Me 2887 2-Isoxazolin-3-yl 2,5-Cl₂—C₆H₃ Me 2888 2-Isoxazolin-3-yl 3,4-Cl₂—C₆H₃ Me 2889 2-Isoxazolin-3-yl 3,5-Cl₂—C₆H₃ Me 2890 2-Isoxazolin-3-yl 3,4-Me₂—C₆H₃ Me 2891 2-Isoxazolin-3-yl 2,4-Me₂—C₆H₃ Me 2892 2-Isoxazolin-3-yl 3-Ph—C₆H₄ Me 2893 2-Isoxazolin-3-yl 4-Ph—C₆H₄ Me 2894 2-Isoxazolin-3-yl Morpholino Me 2895 2-Isoxazolin-3-yl 2,6-Me₂- Me morpholino 2896 2-Isoxazolin-3-yl C₆H₅ Et 2897 2-Isoxazolin-3-yl 4-F—C₆H₄ Et 2898 2-Isoxazolin-3-yl 4-Cl—C₆H₄ Et 2899 2-Isoxazolin-3-yl 4-Me—C₆H₄ Et 2900 2-Isoxazolin-3-yl 3,4-Cl₂—C₆H₃ Et 2901 5-Me-2- C₆H₅ Me isoxazolin-3-yl 2902 5-Me-2- 2-F—C₆H₄ Me isoxazolin-3-yl 2903 5-Me-2- 3-F—C₆H₄ Me isoxazolin-3-yl 2904 5-Me-2- 4-F—C₆H₄ Me isoxazolin-3-yl 2905 5-Me-2- 2-Cl—C₆H₄ Me isoxazolin-3-yl 2906 5-Me-2- 3-Cl—C₆H₄ Me isoxazolin-3-yl 2907 5-Me-2- 4-Cl—C₆H₄ Me isoxazolin-3-yl 2908 5-Me-2- 2-Br—C₆H₄ Me isoxazolin-3-yl 2909 5-Me-2- 3-Br—C₆H₄ Me isoxazolin-3-yl 2910 5-Me-2- 4-Br—C₆H₄ Me isoxazolin-3-yl 2911 5-Me-2- 3-I—C₆H₄ Me isoxazolin-3-yl 2912 5-Me-2- 2-Me—C₆H₄ Me isoxazolin-3-yl 2913 5-Me-2- 3-Me—C₆H₄ Me isoxazolin-3-yl 2914 5-Me-2- 4-Me—C₆H₄ Me isoxazolin-3-yl 2915 5-Me-2- 3-Et—C₆H₄ Me isoxazolin-3-yl 2916 5-Me-2- 4-Et—C₆H₄ Me isoxazolin-3-yl 2917 5-Me-2- 3-MeO—C₆H₄ Me isoxazolin-3-yl 2918 5-Me-2- 4-MeO—C₆H₄ Me isoxazolin-3-yl 2919 5-Me-2- 3-CF₃—C₆H₄ Me isoxazolin-3-yl 2920 5-Me-2- 4-CF₃—C₆H₄ Me isoxazolin-3-yl 2921 5-Me-2- 2,4-F₂—C₆H₃ Me isoxazolin-3-yl 2922 5-Me-2- 2,5-F₂—C₆H₃ Me isoxazolin-3-yl 2923 5-Me-2- 3,4-F₂—C₆H₃ Me isoxazolin-3-yl 2924 5-Me-2- 3,5-F₂—C₆H₃ Me isoxazolin-3-yl 2925 5-Me-2- 2,3-Cl₂—C₆H₃ Me isoxazolin-3-yl 2926 5-Me-2- 2,4-Cl₂—C₆H₃ Me isoxazolin-3-yl 2927 5-Me-2- 2,5-Cl₂—C₆H₃ Me isoxazolin-3-yl 2928 5-Me-2- 3,4-Cl₂—C₆H₃ Me isoxazolin-3-yl 2929 5-Me-2- 3,5-Cl₂—C₆H₃ Me isoxazolin-3-yl 2930 5-Me-2- 3,4-Me—C₆H₃ Me isoxazolin-3-yl 2931 5-Me-2- 2,4-Me₂—C₆H₃ Me isoxazolin-3-yl 2932 5-Me-2- 3-Ph—C₆H₄ Me isoxazolin-3-yl 2933 5-Me-2- 4-Ph—C₆H₄ Me isoxazolin-3-yl 2934 5-Me-2- Morpholino Me isoxazolin-3-yl 2935 5-Me-2- 2,6-Me₂- Me isoxazolin-3-yl morpholino 2936 5-Me-2- C₆H₅ Et isoxazolin-3-yl 2937 5-Me-2- 4-F—C₆H₄ Et isoxazolin-3-yl 2938 5-Me-2- 4-Cl—C₆H₄ Et isoxazolin-3-yl 2939 5-Me-2- 4-Me—C₆H₄ Et isoxazolin-3-yl 2940 5-Me-2- 3,4-Cl₂—C₆H₃ Et isoxazolin-3-yl 2941 Imidazol-1-yl C₆H₅ H ¹H-NMR(CDCl₃) δ ppm: 4.04(3H, S), 5.18(2H, S), 7.03(1H, S), 7.15-7.17(1H, m), 7.29-7.65(9H, m), 7.90(1H, S), 8.05(1H, S) 2942 Imidazol-1-yl 4-F—C₆H₄ H 2943 Imidazol-1-yl 4-Cl—C₆H₄ H mp 92.5-93.0° C. 2944 Imidazol-1-yl 4-Me—C₆H₄ H 2945 Imidazol-1-yl 3,4-Cl₂—C₆H₃ H 2946 1-Me-imidazol-2-yl C₆H₅ H 2947 1-Me-imidazol-2-yl 4-F—C₆H₄ H 2948 1-Me-imidazol-2-yl 4-Cl—C₆H₄ H 2949 1-Me-imidazol-2-yl 4-Me—C₆H₄ H 2950 1-Me-imidazol-2-yl 3,4-Cl₂—C₆H₃ H 2951 1,2,4-Triazol-1-yl C₆H₅ H mp 76.5-77.5° C. 2952 1,2,4-Triazol-1-yl 4-F—C₆H₄ H 2953 1,2,4-Triazol-1-yl 4-Cl—C₆H₄ H 2954 1,2,4-Triazol-1-yl 4-Me—C₆H₄ H 2955 1,2,4-Triazol-1-yl 3,4-Cl₂—C₆H₃ H 2956 5-Me-1,2,4- C₆H₅ H oxadiazol-3-yl 2957 5-Me-1,2,4- 4-F—C₆H₄ H oxadiazol-3-yl 2958 5-Me-1,2,4- 4-Cl—C₆H₄ H oxadiazol-3-yl 2959 5-Me-1,2,4- 4-Me—C₆H₄ H oxadiazol-3-yl 2960 5-Me-1,2,4- 3,4-Cl₂—C₆H₃ H oxadiazol-3-yl 2961 Isoxazol-3-yl C₆H₅ H 2962 Isoxazol-3-yl 4-F—C₆H₄ H 2963 Isoxazol-3-yl 4-Cl—C₆H₄ H 2964 Isoxazol-3-yl 4-Me—C₆H₄ H 2965 Isoxazol-3-yl 3,4-Cl₂—C₆H₃ H 2966 5-Me- C₆H₅ H isoxazol-3-yl 2967 5-Me- 4-F—C₆H₄ isoxazol-3-yl 2968 5-Me- 4-Cl—C₆H₄ H isoxazol-3-yl 2969 5-Me- 4-Me—C₆H₄ H isoxazol-3-yl 2970 5-Me- 3,4-Cl₂—C₆H₃ H isoxazol-3-yl 2971 Isoxazol-5-yl C₆H₅ H 2972 Isoxazol-5-yl 4-F—C₆H₄ H 2973 Isoxazol-5-yl 4-Cl—C₆H₄ H 2974 Isoxazol-5-yl 4-Me—C₆H₄ H 2975 Isoxazol-5-yl 3,4-Cl₂—C₆H₃ H 2976 3-Me- C₆H₅ H isoxazol-5-yl 2977 3-Me- 4-F—C₆H₄ H isoxazoi-5-yl 2978 3-Me- 4-Cl—C₆H₄ H isoxazol-5-yl 2979 3-Me- 4-Me—C₆H₄ H isoxazol-5-yl 2980 3-Me- 3,4-Cl₂—C₆H₃ H isoxazot-5-yl 2981 Oxazol-5-yl C₆H₅ H mp 77-78.5° C. 2982 Oxazol-5-yl 4-F—C₆H₄ H 2983 Oxazol-5-yl 4-Cl—C₆H₄ H 2984 Oxazol-5-yl 4-Me—C₆H₄ H 2985 Oxazol-5-yl 3,4-Cl₂—C₆H₃ H 2986 2-Isoxazolin-3-yl C₆H₅ H 2987 2-Isoxazolin-3-yl 4-F—C₆H₄ H 2988 2-Isoxazolin-3-yl 4-Cl—C₆H₄ H 2989 2-Isoxazolin-3-yl 4-Me—C₆H₄ H 2990 2-Isoxazolin-3-yl 3,4-Cl₂—C₆H₃ H 2991 Thiazolidin-2-yl C₆H₅ H 2992 Thiazolidin-2-yl 4-F—C₆H₄ H 2993 Thiazolidin-2-yl 4-Cl—C₆H₄ H 2994 Thiazolidin-2-yl 4-Me—C₆H₄ H 2995 Thiazolidin-2-yl 3,4-Cl₂—C₆H₃ H 2996 3-Me-thiazolidin- C₆H₅ H 2-yl 2997 3-Me-thiazolidin- 4-F—C₆H₄ H 2-yl 2998 3-Me-thiazolidin- 4-Cl—C₆H₄ H 2-yl 2999 3-Me-thiazolidin- 4-Me—C₆H₄ H 2-yl 3000 3-Me-thiazolidin- 3,4-Cl₂—C₆H₃ H 2-yl 3001 Oxazol-4-yl C₆H₅ Me mp 94.5-96.0° C. 3002 Oxazol-4-yl 4-F—C₆H₄ Me 3003 Oxazol-4-yl 4-Cl—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, S), 4.14(3H, S), 5.22(2H, S), 7.27-7.56(8H, m), 7.77(1H, S), 7.97(1H, S) 3004 Oxazol-4-yl 4-Me—C₆H₄ Me 3005 Oxazol-4-yl 3,4-Cl₂—C₆H₃ Me ¹H-NMR(CDCl₃) δ ppm: 2.01(3H, S), 4.15(3H, S), 5.24(2H, S), 5.50-7.62(6H, m), 7.66(1H, tj=1.2), 7.76(1H, S). 7.97(1H, S) 3006 Oxazol-4-yl C₆H₅ H mp 97-98° C. 3007 Oxazol-4-yl 4-Cl—C₆H₄ H 3008 Oxazol-4-yl C₆H₅ Et 3009 Oxazol-4-yl 4-Cl—C₆H₄ Et 3010 Oxazol-4-yl 3,4-Cl₂—C₆H₃ Et 3011 1-Me-1H- C₆H₅ Me mp 119-120° C. tetrazol-5-yl 3012 1-Me-1H- 4-F—C₆H₄ Me tetrazol-5-yl 3013 1-Me-1H- 4-Cl—C₆H₄ Me tetrazol-5-yl 3014 1-Me-1H- 4-Me—C₆H₄ Me tetrazol-5-yl 3015 1-Me-1H- 3,4-Cl₂—C₆H₃ Me tetrazol-5-yl 3016 Oxazol-4-yl 3-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.07(3H, S), 4.15(3H, S), 5.26(2H, S), 7.35-7.77(8H, m), 7.82(1H, S), 7.97(1H, S) 3017 1-Me-1H- 4-Cl—C₆H₄ H tetrazol-5-yl 3018 1-Me-1H- C₆H₅ Et tetrazol-5-yl 3019 1-Me-1H- 4-Cl—C₆H₄ Et tetrazol-5-yl 3020 Oxazol-4-yl 2,4-Cl₂—C₆H₃ Me ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, S), 4.14(3H, S), 5.22(2H, S), 7.13-7.56(7H, m), 7.78(1H, S), 7.98(1H, S) 3021 1,2,4-Oxadiazol- C₆H₅ Me 5-yl 3022 1,2,4-Oxadiazol- 4-F—C₆H₄ Me 5-yl 3023 1,2,4-Oxadiazol- 4-Cl—C₆H₄ Me 5-yl 3024 1,2,4-Oxadiazol- 4-Me—C₆H₄ Me 5-yl 3025 1,2,4-Oxadiazol- 3,4-Cl₂—C₆H₃ Me 5-yl 3026 1,2,4-Oxadiazol- C₆H₅ H mp 1201-121° C. 5-yl 3027 1,2,4-Oxadiazol- 4-Cl—C₆H₄ H 5-yl 3028 1,2,4-Oxadiazol- C₆H₅ Et 5-yl 3029 1,2,4-Oxadiazol- 4-Cl—C₆H₄ Et 5-yl 3030 1,2,4-Oxadiazol- 3,4-Cl₂—C₆H₃ Et 5-yl 3031 1-Me-1,2,4- C₆H₅ Me triazol-5-yl 3032 1-Me-1,2,4- 4-F—C₆H₄ Me triazol-5-yl 3033 1-Me-1,2,4- 4-Cl—C₆H₄ Me triazol-5-yl 3034 1-Me-1,2,4- 4-Me—C₆H₄ Me triazol-5-yl 3035 1-Me-1,2,4- 3,4-Cl₂—C₆H₃ Me triazol-5-yl 3036 1-Me-1,2,4- C₆H₅ H ¹H-NMR(CDCl₃) δ ppm: triazol-5-yl 4.03(3H, S), 4.12(3H, S), 5.07(2H, S), 7.27-7.55(9H, m), 7.79(1H, S), 7.80(1H, S) 3037 1-Me-1,2,4- 4-Cl—C₆H₄ H triazol-5-yl 3038 1-Me-1,2,4- C₆H₅ Et triazol-5-yl 3039 1-Me-1,2,4- 4-Cl—C₆H₄ Et triazol-5-yl 3040 1-Me-1,2,4- 3,4-Cl₂—C₆H₃ Et triazol-5-yl 3041 Imidazol-1-yl C₆H₅ Me ¹H-NMR(CDCl₃) δ ppm: 2.09(3H, s), 4.03(3H, s), 5.28(2H, s), 7.01(1H, s), 7.14(1H, d, J=2.4), 7.30- 7.62(9H, m), m), 8.03(1H, s) 3042 Imidazol-1-yl 2-F—C₆H₄ Me 3043 Imidazol-1-yl 3-F—C₆H₄ Me 3044 Imidazol-1-yl 4-F—C₆H₄ Me 3045 Imidazol-1-yl 2-Cl—C₆H₄ Me 3046 Imidazol-1-yl 3-Cl—C₆H₄ Me 3047 Imidazol-1-yl 4-Cl—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.07(3H, s), 4.06(3H, s), 5.18(2H, s), 7.01-7.52(10H, m), 8.01(1H, s) 3048 Imidazol-1-yl 2-Br—C₆H₄ Me 3049 Imidazol-1-yl 3-Br—C₆H₄ Me 3050 Imidazoi-1-yl 4-Br—C₆H₄ Me 3051 Imidazol-1-yl 3-I—C₆H₄ Me 3052 Imidazol-1-yl 2-Me—C₆H₄ Me 3053 Imidazol-1-yl 3-Me—C₆H₄ Me 3054 Imidazol-1-yl 4-Me—C₆H₄ Me 3055 Imidazol-1-yl 3-Et—C₆H₄ Me 3056 Imidazol-1-yl 4-Et—C₆H₄ Me 3057 Imidazol-1-yl 3-MeO—C₆H₄ Me 3058 Imidazol-1-yl 4-MeO—C₆H₄ Me 3059 Imidazol-1-yl 3-CF₃—C₆H₄ Me ¹H-NMR(CDCl₃) δ ppm: 2.09(3H, s), 4.04(3H, s), 5.22(2H, s), 7.01(1H, d, J=1.2), 7.15(1 H, d, J=1.2), 7.35-7.85(8H, m), 8.02(1H, s) 3060 Imidazol-1-yl 4-CF₃—C₆H₄ Me 3061 Imidazol-1-yl 2,4-F₂—C₆H₃ Me 3062 Imidazol-1-yl 2,5-F₂—C₆H₃ Me 3063 Imidazol-1-yl 3,4-F₂—C₆H₃ Me 3064 Imidazol-1-yl 3,5-F₂—C₆H₃ Me 3065 Imidazol-1-yl 2,3-Cl₂—C₆H₃ Me 3066 Imidazol-1-yl 2,4-Cl₂—C₆H₃ Me ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 4.03(3H, s), 5.16(2H, s), 7.02(1H, s), 7.13-7.52(8H, m), 8.01(1H, s) 3067 Imidazol-1-yl 2,5-Cl₂—C₆H₃ Me 3068 Imidazol-1-yl 3,4-Cl₂—C₆H₃ Me ¹H-NMR(CDCl₃) δ ppm: 2.03(3H, s), 4.04(3H, s), 5.19(2H, s), 7.01(1H, s), 7.13-7.52(7H, m), 7.66(1H, s), 8.01(1H, s) 3069 Imidazol-1-yl 3,5-Cl₂—C₆H₃ Me 3070 Imidazol-1-yl 3,4-Me₂—C₆H₃ Me 3071 Imidazol-1-yl 2,4-Me₂—C₆H₃ Me 3072 Imidazol-1-yl 3-Ph—C₆H₄ Me 3073 Imidazol-1-yl 4-Ph—C₆H₄ Me 3074 Imidazol-1-yl Morpholino Me 3075 Imidazol-1-yl 2,6-Me₂- Me morpholino 3076 Imidazol-1-yl C₆H₅ Et 3077 Imidazol-1-yl 4-F—C₆H₄ Et 3078 Imidazol-1-yl 4-Cl—C₆H₄ Et 3079 Imidazol-1-yl 4-Me—C₆H₄ Et 3080 Imidazol-1-yl 3,4-Cl₂—C₆H₃ Et 3081 1-Me-imidazol-2-yl C₆H₅ Me 3082 1-Me-imidazol-2-yl 2-F—C₆H₄ Me 3083 1-Me-imidazol-2-yl 3-F—C₆H₄ Me 3084 1-Me-imidazol-2-yl 4-F—C₆H₄ Me 3085 1-Me-imidazol-2-yl 2-Cl—C₆H₄ Me 3086 1-Me-imidazol-2-yl 3-Cl—C₆H₄ Me 3087 1-Me-imidazol-2-yl 4-Cl—C₆H₄ Me 3088 1-Me-imidazol-2-yl 2-Br—C₆H₄ Me 3089 1-Me-imidazol-2-yl 3-Br—C₆H₄ Me 3090 1-Me-imidazol-2-yl 4-Br—C₆H₄ Me 3091 1-Me-imidazol-2-yl 3-I—C₆H₄ Me 3092 1-Me-imidazol-2-yl 2-Me—C₆H₄ Me 3093 1-Me-imidazol-2-yl 3-Me—C₆H₄ Me 3094 1-Me-imidazol-2-yl 4-Me—C₆H₄ Me 3095 1-Me-imidazol-2-yl 3-Et—C₆H₄ Me 3096 1-Me-imidazol-2-yl 4-Et—C₆H₄ Me 3097 1-Me-imidazol-2-yl 3-MeO—C₆H₄ Me 3098 1-Me-imidazol-2-yl 4-MeO—C₆H₄ Me 3099 1-Me-imidazol-2-yl 3-CF₃—C₆H₄ Me 3100 1-Me-imidazol-2-yl 4-CF₃—C₆H₄ Me 3101 Imidazol-1-yl Me Me ¹H-NMR(CDCl₃) δ ppm: 1.70(3H, s), 1.78(3H, s), 4.03(3H, s), 5.01(2H, s), 7.02(1H, s), 7.16(1H, d, J=1.2), 7.31-7.49(4H, m), 7.99(1H, s) 3102 Imidazol-1-yl Cyclohexyl Me 3103 Imidazol-1-yl t-Bu Me 3104 Imidazol-1-yl 5-Me- Me isoxazol-3-yl 3105 Imidazol-1-yl Pyridin-3-yl Me 3106 1-Me-imidazol-2-yl Me Me 3107 1-Me-imidazol-2-yl Cyclohexyl Me 3108 1-Me-imidazol-2-yl t-Bu Me 3109 1-Me-imidazol-2-yl 5-Me- Me isoxazol-3-yl 3110 1-Me-imidazol-2-yl Pyridin-3-yl Me 3111 Isoxazol-3-yl Me Me 3112 Isoxazol-3-yl Cyclohexyl Me 3113 Isoxazol-3-yl t-Bu Me 3114 Isoxazol-3-yl 5-Me- Me isoxazol-3-yl 3115 Isoxazol-3-yl Pyridin-3-yl Me 3116 5-Me- Me Me isoxazol-3-yl 3117 5-Me- Cyclohexyl Me isoxazol-3-yl 3118 5-Me- t-Bu Me isoxazol-3-yl 3119 5-Me- 5-Me- Me isoxazol-3-yl isoxazol-3-yl 3120 5-Me- Pyridin-3-yl Me isoxazol-3-yl 3121 3-Me- Me Me isoxazol-5-yl 3122 3-Me- Cyclohexyl Me isoxazol-5-yl 3123 3-Me- t-Bu Me isoxazol-5-yl 3124 3-Me- 5-Me- Me isoxazol-5-yl isoxazol-3-yl 3125 3-Me- Pyridin-3-yl Me isoxazol-5-yl 3126 1,3,4-Oxadiazol- Me Me 2-yl 3127 1,3,4-Oxadiazol- Cyclohexyl Me 2-yl 3128 1,3,4-Oxadiazol- t-Bu Me 2-yl 3129 1,3,4-Oxadiazol- 5-Me- Me 2-yl isoxazol-3-yl 3130 1,3,4-Oxadiazol- Pyridin-3-yl Me 2-yl 3131 Thiazolidin-2-yl Me Me 3132 Thiazolidin-2-yl Cyclohexyl Me 3133 Thiazolidin-2-yl t-Bu Me 3134 Thiazolidin-2-yl 5-Me- Me isoxazol-3-yl 3135 Thiazolidin-2-yl Pyridin-3-yl Me 3136 Pyrazol-1-yl C₆H₅ H ¹H-NMR(CDCl₃) δ ppm: 4.03(3H, s), 4.93(2H, s), 6.43(1H, t, J=2.4), 7.31- 7.60(10H, m), 7.99(1H, s), 8.51(1H, d, J=2.4) 3137 Pyrazol-1-yl C₆H₅ Me 3138 Pyrazol-1-yl 4-F—C₆H₄ Me 3139 Pyrazol-1-yl 4-Cl—C₆H₄ Me 3140 Pyrazol-1-yl 4-Me—C₆H₄ Me

[0712] The following Test Examples illustrate the effects of the fungicide of the present invention. (I. Controlling effects on various plant diseases by foliage application (pot experiment))

Experimental Method

[0713] A test compound was dissolved in a small amount of N,N-dimethylformamide, and the solution was diluted to a given concentration with distilled water containing a spreader. Thus, a liquid sample to be tested was prepared. The liquid sample was sprayed to test plants, and 24 hours thereafter, pathogens were inoculated by the method described below.

[0714] The percent control was calculated according to the following equation:

Percent control (%)=100×severity, number of lesions, etc. in untreated plot−severity, number of lesions, etc. in treated plot/severity, number of lesions, etc. in untreated plot

Test Example 1

[0715] Controlling Effect on Pyricularia oryzae

[0716] Two-week rice seedlings (cv.: AICHIASAHI) were transplanted in plastic cups (each 9 cm in diameter) and cultivated further 2 weeks. The test compound in the form of a solution or a suspension was sprayed to the foliage of the rice seedlings, to which a conidia suspension of Pyricularia oryzae cultured in an oatmeal medium was inoculated by spraying. After the inoculation, the test plant was kept in a moist chamber (28° C., 100% R.H.) for 24 hours, followed by cultivation in a greenhouse for 5 days. Six days after the inoculation, the number of lesions on the leaves of the inoculated plant was measured to calculate the percent control.

[0717] The results are as follows. Controlling effect on Pyricularia orvzae by foliage application at 500 Compound No. ppm (percent control)   1 90   5 97   6 90   7 97  13 90  15 90  16 90  39 70  40 90  61 97  81 97  105A 97  106A 97  107A 90  112A 97  113A 97  114A 90  118B 70  122A 97  131A 90  132A 70  136A 90  136B 70  141A 70  141B 70  146A 97  201 90  205 90  206 90  207 90  215 70  221 70  225 70  226 70  241 70  261 70  266 90  267 90  281 70  287 90  295 90  300 70  305 70  306 70  312 70  313 90  314 90  322 90  336 70  436 70  512A 90  512B 97  536B 70  541B 70  605A 90  607A 90  612A 90  613A 70  614B 70  636A 97  636B 70  641A 70  690A 97  705 70  706 70  712 90  713 97  716 70  722 90  731 70  732 70  741 70  801 70  812 70  912 70  936A 97 1112 97 1236 97 1310 70 1328 90 1460 90 1461 70 1554A 70 1581 70 1584 70 1674 70 2799 100  2839 90 3041 90 Reference Fthalide 97

Test Example 2

[0718] Controlling Effect on Sphaerotheca fuliginea

[0719] Seeds of cucumber (cv.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The liquid test sample in the form of a solution or suspension was sprayed on the surface of their first leaves. The pathogen was inoculated to the leaves by spraying a conidia suspension of Sphaerotheca fuliginea which had been cultured on the cucumber leaves. After the inoculation, the plants were kept in a greenhouse at 20° C. for 10 days. Then, the infected area on the leaf was observed, and the percent control was calculated.

[0720] The results are as follows. Controlling effect on Sphaerotheca fuliginea by foliage application at Compound No. 500 ppm (percent control)   1 100   5 100   7 100  13 100  15 100  16 100  39 100  40 100  57  90  101A  70  104A  97  105A 100  106A 100  106B  97  107A 100  112A 100  112B  90  113A 100  113B  90  114A 100  119A  97  122A 100  122B 100  130A 100  131A 100  131B 100  132A 100  136A 100  136B 100  141A 100  141B 100  144A 100  144B  70  146A  97  161 100  201 100  205 100  206 100  207 100  215 100  221  97  226  70  227  97  261  97  266  97  267 100  270  97  275 100  278  97  294  97  300  70  305 100  306  97  312 100  313 100  314 100  322 100  336 100  412 100  436 100  512A 100  512B 100  536A  90  536B 100  541A 100  541B 100  605A 100  605B 100  606A 100  606B  90  607A  97  607B  97  612A 100  612B 100  613A 100  613B  97  614B  97  636A 100  636B 100  641A 100  641B 100  690A 100  690B 100  701  97  705 100  706 100  707 100  712 100  713 100  716 100  722 100  731 100  732 100  736 100  741 100  801 100  805  97  807 100  812 100  836A 100  836B 100  844  97  905  90  912 100  936A 100  936B  97 1112 100 1114  70 1121 100 1122B 100 1123  97 1136 100 1161  70 1236 100 1304  70 1310  90 1311  70 1312  70 1328 100 1341A  70 1341B  70 1428 100 1478  70 1514  97 1515  70 1581  70 1854 100 1590  70 1634A 100 1634B  70 1674  70 1721 100 1734  90 1735 100 1826  70 2001  70 2012 100 2014 100 2036 100 2044  97 2120  70 2507 100 2528 100 2799 100 2839 100 3041  97 Reference Fenarimol  97

Test Example 3

[0721] Controlling Effect on Botrytis cinerea

[0722] The seeds of cucumber (cv.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the surface of their first leaves, and mycelial disks (4 mm φ) of Botrytis cinerea cultured on the potato sucrose agar medium were put on the leaf surfaces to inoculate the cucumber seedlings with the pathogen. The plants were kept in a moist chamber at 20° C. for 3 days. The diameter of the lesions on the leaves was measured and the percent control was calculated.

[0723] The results are as follows. Controlling effect on Botrytis cinerea by foliage application at 500 ppm Compound No. (percent control)  1 100  5  70  6 100  7 100  13  70  15 100  40  70  61 100  81  90 106A  70 122A  70 130A  70 132A  70 141A  90 144A  70 201  70 205  70 206  97 207 100 215  97 314  70 605A  70 607A  70 713  70 732  70 741  90 Reference Fenarimol  97

Test Example 4

[0724] Controlling Effect on Erysiphe araminis f. sp. tritici

[0725] The seeds of wheat (cv.: NOR¹ N No. 61) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the seedlings, and conidia of Erysiphe graminis f. sp. tritici cultured on wheat leaves were dropped on the test plants to inoculate the plants with the pathogen. After the inoculation, the plants were kept in a greenhouse at 20° C. for 10 days. The infected area on the leaf was observed, and the percent control was calculated.

[0726] The results are as follows. Controlling effect on Erysiphe graminis f. sp. tritici by foliage application at 500 ppm Compound No. (percent control)   1 90   5 90   6 100    7 100   13 90  15 97  16 90  40 97  57 70  61 97  81 97  104A 90  104B 70  105A 70  106A 70  107A 70  112A 100   113A 90  114A 90  122A 97  131A 90  132A 70  136A 90  136B 70  141A 90  161 70  201 90  206 90  207 100   215 90  221 70  226 70  227 70  235 90  261 97  265 70  266 97  267 97  270 90  275 90  278 90  281 90  295 90  305 90  306 70  312 100   313 70  314 70  322 70  336 97  412 70  436 90  512A 97  512B 97  536A 97  536B 100   541A 90  541B 90  605A 90  605B 90  606A 70  607A 90  607B 70  612A 100   612B 100   613A 90  613B 70  614B 70  636A 100   636B 100   641A 90  641B 90  690A 100   690B 100   701 70  706 90  707 90  712 100   713 90  716 70  722 90  731 70  732 70  736 100   741 90  801 90  812 100   836A 97  836B 97  912 90  936A 97  936B 90 1101 90 1112 90 1114 70 1121 90 1122A 70 1122B 90 1123 90 1136 90 1161 90 1236 90 1310 90 1311 70 1328 90 1341A 90 1341B 90 1428 70 1455 70 1460 90 1478 90 1514 70 1515 90 1554A 70 1554B 70 1584 100  1634A 97 1654 70 1665 70 1667 70 1674 70 1721 90 1734 70 1735 97 1829 90 2012 70 2036 90 2799 97 2839 97 Reference Fenarimol 97

Test Example 5

[0727] Controlling Effect on Puccinia coronata

[0728] The seeds of oat (cv.: PC-38) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the seedlings. Spores of Puccinia coronata cultured on oat leaves were collected, diluted about 10-fold with talc, and sprayed to the test plants to inoculate the plants with the pathogen. After the inoculation, the plants were kept in a moist chamber at 20° C. for 1 day and then in a greenhouse at 20° C. for 8 days. The infected area on the leaf was observed, and the percent control was calculated.

[0729] The results are as follows. Controlling effect on Puccinia coronata by foliage application Compound No. at 500 ppm (percent control)   1 97   5 90   6 100    7 97  13 97  15 100   16 100   40 70  57 90  61 97  81 97  112A 100   136A 100   136B 97  161 97  201 90  205 70  206 97  207 97  215 90  267 90  275 90  278 90  298 70  312 97  336 100   436 90  536A 90  536B 97  612A 97  636A 100   636B 90  701 97  712 100   722 97  736 100   801 97  914 97  936A 90 1001 70 1112 70 1113 70 1136 90 1236 97 1328 70 1478 70 1584 70 1721 70 2001 70 Reference Fenarimol 97

Test Example 6

[0730] Controlling Effect on Pseudoperonospora cubensis

[0731] The seeds of cucumber (var.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the surface of their first leaves, and a zoosporangia suspension of Pseudoperonospora cubensis cultured on cucumber leaves was dropped on the above leaf surfaces to inoculate the test plants with the pathogen. After the inoculation, the plants were kept in a moist chamber at 20° C. for 10 days. Then, the area of the lesions around the inoculum were observed and the percent control was calculated.

[0732] The results are as follows. Controlling effect on Pseudoperonospora cubensis by foliage application at 500 ppm Compound No. (percent control)  105A 100  106A 100  106B 100  112A  97  113A 100  119A  85  122A 100  130A 100  131A 100  132A 100  141A 100  144A 100  146A 100  305 100  306 100  313 100  314 100  412 100  512A 100  512B 100  536B 100  541A 100  541B 100  605A 100  606A  95  606B 100  607A  97  607B  97  612A 100  612B 100  613A  70  613B 100  614B 100  641A 100  690A 100  690B 100  701 100  705 100  706 100  713 100  716 100  722 100  731 100  732 100  741 100  801 100  844 100  905  99 1721 100 2014 100 2044 100 2507 100 2528 100 2799  95 2839  95 Reference Benalaxyl  97

[0733] As described above, the present invention provides a novel oxime derivative, particularly a heterocyclic compound substituted with α-(O-substituted oxyimino)-2-substituted benzyl, having potent fungicidal activity, a process for producing it, intermediates therefor, and a fungicide containing it as an active ingredient. 

1. A compound of the formula (I):

wherein R¹ is optionally substituted aryl, an optionally substituted heterocyclic group, mono or di-substituted methyleneamino, optionally substituted (substituted imino)methyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, substituted carbonyl or substituted sulfonyl; R² is alkyl, alkenyl, alkynyl or cycloalkyl; R³ is an optionally substituted heterocyclic group; R⁴ is hydrogen, alkyl, alkoxy, halogen, nitro, cyano or halogenated alkyl; M is an oxygen atom, S(O)_(i) (in which i is 0, 1 or 2), NR¹⁶ (in which R¹⁶ is hydrogen, alkyl or acyl) or a single bond; n is 0 or 1, provided that, when R³ is imidazol-1-yl or 1H-1,2,4-triazol-1-yl, n is 1; and˜indicates an E- or Z-isomer or a mixture thereof; or a salt thereof.
 2. A compound according to claim 1, wherein the optionally substituted heterocyclic group represented by R¹ is pyridyl, pyrimidinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, pyridazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, triazolyl, quinolyl, indolyl, benzisothiazolyl, benzisoxazolyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof.
 3. A compound according to claim 1, wherein R¹ is phenyl or a heterocyclic group, each of which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro, or a salt thereof.
 4. A compound according to claim 1, wherein R¹ is phenyl; phenyl substituted with halogen and/or lower alkyl; or pyridyl substituted with halogen and/or halogenated lower alkyl; or a salt thereof.
 5. A compound according to claim 1, wherein R¹ is phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 4-chloro-2-methylphenyl, 2-chloropyridin-3-yl, 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl or 3-trifluoromethyl-5-chloropyridin-2-yl, or a salt thereof.
 6. A compound according to claim 1, wherein R¹ is a group of the formula (a):

wherein R⁹ and R¹⁰ are the same or different and are hydrogen, optionally substituted alkyl, acyl, alkylthio, alkylsulfinyl alkylsulfonyl, optionally substituted amino, cycloalkyl, optionally substituted aryl or an optionally substituted heterocyclic group, or R⁹ and R¹⁰ are linked together to form a monocyclic or polycyclic ring which may contain a heteroatom, or a salt thereof.
 7. A compound according to claim 1, wherein R⁹ and R¹⁰ are the same or different and are hydrogen, alkyl, haloalkyl, alkoxyalkyl, alkylcarbonyl, optionally substituted phenyl, optionally substituted naphthyl or an optionally substituted heterocyclic group, or R⁹ and R¹⁰ are linked together to form a cyclopentane or cyclohexane ring which may form a condensed ring with another ring, or a salt thereof.
 8. A compound according to claim 1, wherein R⁹ is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl and cyano, or a salt thereof.
 9. A compound according to claim 1, wherein R⁹ is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of chlorine, methyl, trifluoromethyl and methoxy, or a salt thereof.
 10. A compound according to claim 1, wherein R⁹ is morpholino, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof.
 11. A compound according to claim 1, wherein R¹⁰ is hydrogen or alkyl, or a salt thereof.
 12. A compound according to claim 1, wherein R¹⁰ is hydrogen, methyl or ethyl, or a salt thereof.
 13. A compound according to claim 1, wherein R² is alkyl or alkenyl, or a salt thereof.
 14. A compound according to claim 1, wherein R² is methyl, ethyl or allyl, or a salt thereof.
 15. A compound according to claim 1, wherein R³ is isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiazolinyl, isoxazolinyl, imidazolinyl, oxazolinyl or thiazolidinyl, each of which is unsubstituted or substituted, or a salt thereof.
 16. A compound according to claim 1, wherein R³ is imidazolyl; imidazolyl substituted with lower alkyl; imidazolinyl; triazolyl; imidazolinyl substituted with lower alkyl; isoxazolyl; isoxazolyl substituted with lower alkyl; oxadiazolyl; oxadiazolyl substituted with lower alkyl; isoxazolinyl; isoxazolinyl substituted with lower alkyl; oxazolinyl; pyrazolyl; pyrazolyl substituted with lower alkyl; thiazolinyl; furyl; tetrazolyl substituted with lower alkyl; oxazolyl; isothiazolyl substituted with lower alkyl; thiazolidinyl; or thiazolidinyl substituted with lower alkyl; or a salt thereof.
 17. A compound according to claim 1, wherein R³ is imidazol-1-yl, imidazol-2-yl, 1-methylimidazol-2-yl, 2-methylimidazol-1-yl, 4-methylimidazol-1-yl, 5-methylimidazol-1-yl, 2-imidazolin-2-yl, 1H-1,2,4-triazol-1-yl, 1-methyl-2-imidazolin-2-yl, isoxazol-3-yl, 3-methylisoxazol-5-yl, 5-methylisoxazol-3-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 2-isoxazolin-3-yl, 2-oxazolin-2-yl, 3-methyl-2-isoxazolin-5-yl, pyrazol-1-yl, 1-methylpyrazol-5-yl, 2-thiazolin-2-yl, 2-furyl, 3-methylisothiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 2-methyltetrazol-5-yl, oxazol-5-yl, isoxazol-5-yl, thiazolidin-2-yl or 3-methylthiazolidin-2-yl, or a salt thereof.
 18. A compound according to claim 1, wherein R⁴ is hydrogen, or a salt thereof.
 19. A compound according to claim 1, wherein M is an oxygen atom, or a salt thereof.
 20. A compound according to claim 19, wherein R¹ is phenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 1); R¹ is 4-chlorophenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 7); R¹ is 2-methylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 13); R¹ is 4-methylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 15); R¹ is 2-ethylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 16); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 39); R¹ is phenyl, R² is ethyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 61); R¹ is phenyl, R² is allyl, R³ is imidazol-1-yl, R⁴ is hydrogen, and n is 1 (Compound No. 81); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 1-methylimidazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 136); R¹ is 4-chloro-2-methylphenyl, R² is methyl, R³ is 1-methylimidazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 141); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 336); R¹ is 5-trifluoromethylpyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 387); R¹ is 5-trifluoromethyl-3-chloropyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 390); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 5-methylisoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 436); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 3-methylisoxazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 636); R¹ is 5-trifluoromethyl-3-chloropyridin-2-yl, R² is methyl, R³ is 3-methylisoxazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 690); R¹ is 2-methylphenyl, R² is methyl, R³ is 1,3,4-oxadiazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 712); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 1,3,4-oxadiazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 736); R¹ is 4-chloro-2-methylphenyl, R² is methyl, R³ is 1,3,4-oxadiazol-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 741); R¹ is 4-chlorophenyl, R² is methyl, R³ is 1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 807); R¹ is 2-methylphenyl, R² is methyl, R³ is 1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 812); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 836); R¹ is 2-methylphenyl, R² is methyl, R³ is 5-methyl-1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 912); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 5-methyl-1,2,4-oxadiazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 936); R¹ is 2,5-dimethyl phenyl, R² is methyl, R³ is 5 -methyl-2-imidazolin-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 1136); R¹ is 4-chlorophenyl, R² is methyl, R³ is 1,2,4-oxadiazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 1584); R¹ is 2,5-dimethylphenyl, R² is methyl, R³ is 2-methyl-2H-tetrazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2036); R¹ is 3,5-dichloropyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2276); R¹ is 5-chloro-3-trifluoromethylpyridin-2-yl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2306); R¹ is a group represented by the formula (a), R⁹ is 4-chlorophenyl, R¹⁰ is methyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2387); R¹ is a group of by the formula (a), R⁹ is 3-trifluoromethylphenyl, R¹⁰ is methyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2399); R¹ is a group of the formula (a), R⁹ is 3,4-dichlorophenyl, R¹⁰ is methyl, R² is methyl, R³ is isoxazol-3-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2408); R¹ is a group represented by the formula (a), R⁹ is 4-chlorophenyl, R¹⁰ is methyl, R² is methyl, R³ is 3-methylisoxazol-5-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2507); R¹ is a group of the formula (a), R⁹ is 3-trifluoromethylphenyl, R¹⁰ is methyl, R² is methyl, R³ is thiazolidin-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2799); or R¹ is a group of the formula (a), R⁹ is 3-trifluoromethylphenyl, R¹⁰ is methyl, R² is methyl, R³ is 3-methylthiazolidin-2-yl, R⁴ is hydrogen, and n is 1 (Compound No. 2839).
 21. A fungicidal composition comprising a compound according to any one of claims 1 to 20 or a salt thereof as an active ingredient.
 22. A process for producing a compound of the formula (I):

wherein each symbol is as defined in claim 1, which comprises reacting the compound of the formula (V):

wherein A is halogen and the other symbols are as defined in claim 1, with a compound of the formula (X): R³—H   (X) wherein R³ is an optionally substituted heterocyclic group.
 23. A process according to claim 22, wherein R³ is pyrrolyl, imidazolyl, pyrazolyl or triazolyl, each of which is unsubstituted or substituted.
 24. A compound of the formula (V):

wherein A is halogen and the other symbols are as defined in claim 1, or a salt thereof.
 25. A compound according to claim 24, wherein M is an oxygen atom, or a salt thereof.
 26. A compound of the formula (XIV):

wherein each symbol is as defined in claim 1, provided that, when M is an oxygen atom and R³ is isoxazol-4-yl, n is 1, or a salt thereof.
 27. A compound according to claim 26, wherein M is an oxygen atom, or a salt thereof.
 28. A compound of the formula (XLVIII):

wherein P is a protective group of a hydroxyl group, and the other symbols are as defined in claim 1, or a salt thereof.
 29. A method for controlling or preventing phytopathogenic fungi which comprises applying as an active ingredient a compound according to claim 1 to a locus where phytopathogenic fungi propagate or will propagate.
 30. Use of a compound according to claim 1 in the manufacture of a fungicidal composition. 